document_title: Action potential

question_text: where does action potential start in a neuron

question_tokens: where does action potential start in a neuron

text: Action potential

text: Overview[edit]

text: Nearly all cell membranes in animals, plants and fungi maintain a voltage difference between the exterior and interior of the cell, called the membrane potential. A typical voltage across an animal cell membrane is –70 mV. This means that the interior of the cell has a negative voltage of approximately one-fifteenth of a volt relative to the exterior. In most types of cells, the membrane potential usually stays fairly constant. Some types of cells, however, are electrically active in the sense that their voltages fluctuate over time. In some types of electrically active cells, including neurons and muscle cells, the voltage fluctuations frequently take the form of a rapid upward spike followed by a rapid fall. These up-and-down cycles are known as action potentials. In some types of neurons, the entire up-and-down cycle takes place in a few thousandths of a second. In muscle cells, a typical action potential lasts about a fifth of a second. In some other types of cells, and also in plants, an action potential may last three seconds or more.

text: The electrical properties of a cell are determined by the structure of the membrane that surrounds it. A cell membrane consists of a lipid bilayer of molecules in which larger protein molecules are embedded. The lipid bilayer is highly resistant to movement of electrically charged ions, so it functions as an insulator. The large membrane-embedded proteins, in contrast, provide channels through which ions can pass across the membrane. Action potentials are driven by channel proteins whose configuration switches between closed and open states as a function of the voltage difference between the interior and exterior of the cell. These voltage-sensitive proteins are known as voltage-gated ion channels.

text: Process in a typical neuron[edit]

text: All cells in animal body tissues are electrically polarized – in other words, they maintain a voltage difference across the cell's plasma membrane, known as the membrane potential. This electrical polarization results from a complex interplay between protein structures embedded in the membrane called ion pumps and ion channels. In neurons, the types of ion channels in the membrane usually vary across different parts of the cell, giving the dendrites, axon, and cell body different electrical properties. As a result, some parts of the membrane of a neuron may be excitable (capable of generating action potentials), whereas others are not. Recent studies[citation needed] have shown that the most excitable part of a neuron is the part after the axon hillock (the point where the axon leaves the cell body), which is called the initial segment, but the axon and cell body are also excitable in most cases.

text: Each excitable patch of membrane has two important levels of membrane potential: the resting potential, which is the value the membrane potential maintains as long as nothing perturbs the cell, and a higher value called the threshold potential. At the axon hillock of a typical neuron, the resting potential is around –70 millivolts (mV) and the threshold potential is around –55 mV. Synaptic inputs to a neuron cause the membrane to depolarize or hyperpolarize; that is, they cause the membrane potential to rise or fall. Action potentials are triggered when enough depolarization accumulates to bring the membrane potential up to threshold. When an action potential is triggered, the membrane potential abruptly shoots upward and then equally abruptly shoots back downward, often ending below the resting level, where it remains for some period of time. The shape of the action potential is stereotyped; this means that the rise and fall usually have approximately the same amplitude and time course for all action potentials in a given cell. (Exceptions are discussed later in the article). In most neurons, the entire process takes place in about a thousandth of a second. Many types of neurons emit action potentials constantly at rates of up to 10–100 per second. However, some types are much quieter, and may go for minutes or longer without emitting any action potentials.

text: Biophysical basis[edit]

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text: Action potentials result from the presence in a cell's membrane of special types of voltage-gated ion channels.[2] A voltage-gated ion channel is a cluster of proteins embedded in the membrane that has three key properties:

text:
It is capable of assuming more than one conformation.
At least one of the conformations creates a channel through the membrane that is permeable to specific types of ions.
The transition between conformations is influenced by the membrane potential.

text: Thus, a voltage-gated ion channel tends to be open for some values of the membrane potential, and closed for others. In most cases, however, the relationship between membrane potential and channel state is probabilistic and involves a time delay. Ion channels switch between conformations at unpredictable times: The membrane potential determines the rate of transitions and the probability per unit time of each type of transition.

text: Voltage-gated ion channels are capable of producing action potentials because they can give rise to positive feedback loops: The membrane potential controls the state of the ion channels, but the state of the ion channels controls the membrane potential. Thus, in some situations, a rise in the membrane potential can cause ion channels to open, thereby causing a further rise in the membrane potential. An action potential occurs when this positive feedback cycle proceeds explosively. The time and amplitude trajectory of the action potential are determined by the biophysical properties of the voltage-gated ion channels that produce it. Several types of channels capable of producing the positive feedback necessary to generate an action potential do exist. Voltage-gated sodium channels are responsible for the fast action potentials involved in nerve conduction. Slower action potentials in muscle cells and some types of neurons are generated by voltage-gated calcium channels. Each of these types comes in multiple variants, with different voltage sensitivity and different temporal dynamics.

text: The most intensively studied type of voltage-dependent ion channels comprises the sodium channels involved in fast nerve conduction. These are sometimes known as Hodgkin-Huxley sodium channels because they were first characterized by Alan Hodgkin and Andrew Huxley in their Nobel Prize-winning studies of the biophysics of the action potential, but can more conveniently be referred to as NaV channels. (The "V" stands for "voltage".) An NaV channel has three possible states, known as deactivated, activated, and inactivated. The channel is permeable only to sodium ions when it is in the activated state. When the membrane potential is low, the channel spends most of its time in the deactivated (closed) state. If the membrane potential is raised above a certain level, the channel shows increased probability of transitioning to the activated (open) state. The higher the membrane potential the greater the probability of activation. Once a channel has activated, it will eventually transition to the inactivated (closed) state. It tends then to stay inactivated for some time, but, if the membrane potential becomes low again, the channel will eventually transition back to the deactivated state. During an action potential, most channels of this type go through a cycle deactivated→activated→inactivated→deactivated. This is only the population average behavior, however — an individual channel can in principle make any transition at any time. However, the likelihood of a channel's transitioning from the inactivated state directly to the activated state is very low: A channel in the inactivated state is refractory until it has transitioned back to the deactivated state.

text: The outcome of all this is that the kinetics of the NaV channels are governed by a transition matrix whose rates are voltage-dependent in a complicated way. Since these channels themselves play a major role in determining the voltage, the global dynamics of the system can be quite difficult to work out. Hodgkin and Huxley approached the problem by developing a set of differential equations for the parameters that govern the ion channel states, known as the Hodgkin-Huxley equations. These equations have been extensively modified by later research, but form the starting point for most theoretical studies of action potential biophysics.

text: As the membrane potential is increased, sodium ion channels open, allowing the entry of sodium ions into the cell. This is followed by the opening of potassium ion channels that permit the exit of potassium ions from the cell. The inward flow of sodium ions increases the concentration of positively charged cations in the cell and causes depolarization, where the potential of the cell is higher than the cell's resting potential. The sodium channels close at the peak of the action potential, while potassium continues to leave the cell. The efflux of potassium ions decreases the membrane potential or hyperpolarizes the cell. For small voltage increases from rest, the potassium current exceeds the sodium current and the voltage returns to its normal resting value, typically −70 mV.[3][4][5] However, if the voltage increases past a critical threshold, typically 15 mV higher than the resting value, the sodium current dominates. This results in a runaway condition whereby the positive feedback from the sodium current activates even more sodium channels. Thus, the cell fires, producing an action potential.[3][6][7][note 1] The frequency at which cellular action potentials are produced is known as its firing rate.

text: Currents produced by the opening of voltage-gated channels in the course of an action potential are typically significantly larger than the initial stimulating current. Thus, the amplitude, duration, and shape of the action potential are determined largely by the properties of the excitable membrane and not the amplitude or duration of the stimulus. This all-or-nothing property of the action potential sets it apart from graded potentials such as receptor potentials, electrotonic potentials, and synaptic potentials, which scale with the magnitude of the stimulus. A variety of action potential types exist in many cell types and cell compartments as determined by the types of voltage-gated channels, leak channels, channel distributions, ionic concentrations, membrane capacitance, temperature, and other factors.

text: The principal ions involved in an action potential are sodium and potassium cations; sodium ions enter the cell, and potassium ions leave, restoring equilibrium. Relatively few ions need to cross the membrane for the membrane voltage to change drastically. The ions exchanged during an action potential, therefore, make a negligible change in the interior and exterior ionic concentrations. The few ions that do cross are pumped out again by the continuous action of the sodium–potassium pump, which, with other ion transporters, maintains the normal ratio of ion concentrations across the membrane. Calcium cations and chloride anions are involved in a few types of action potentials, such as the cardiac action potential and the action potential in the single-cell alga Acetabularia, respectively.

text: Although action potentials are generated locally on patches of excitable membrane, the resulting currents can trigger action potentials on neighboring stretches of membrane, precipitating a domino-like propagation. In contrast to passive spread of electric potentials (electrotonic potential), action potentials are generated anew along excitable stretches of membrane and propagate without decay.[8] Myelinated sections of axons are not excitable and do not produce action potentials and the signal is propagated passively as electrotonic potential. Regularly spaced unmyelinated patches, called the nodes of Ranvier, generate action potentials to boost the signal. Known as saltatory conduction, this type of signal propagation provides a favorable tradeoff of signal velocity and axon diameter. Depolarization of axon terminals, in general, triggers the release of neurotransmitter into the synaptic cleft. In addition, backpropagating action potentials have been recorded in the dendrites of pyramidal neurons, which are ubiquitous in the neocortex.[c] These are thought to have a role in spike-timing-dependent plasticity.

text: Maturation of the electrical properties of the action potential[edit]

text: A neuron's ability to generate and propagate an action potential changes during development. How much the membrane potential of a neuron changes as the result of a current impulse is a function of the membrane input resistance. As a cell grows, more channels are added to the membrane, causing a decrease in input resistance. A mature neuron also undergoes shorter changes in membrane potential in response to synaptic currents. Neurons from a ferret lateral geniculate nucleus have a longer time constant and larger voltage deflection at P0 than they do at P30.[9] One consequence of the decreasing action potential duration is that the fidelity of the signal can be preserved in response to high frequency stimulation. Immature neurons are more prone to synaptic depression than potentiation after high frequency stimulation.[9]

text: In the early development of many organisms, the action potential is actually initially carried by calcium current rather than sodium current. The opening and closing kinetics of calcium channels during development are slower than those of the voltage-gated sodium channels that will carry the action potential in the mature neurons. The longer opening times for the calcium channels can lead to action potentials that are considerably slower than those of mature neurons.[9] Xenopus neurons initially have action potentials that take 60–90 ms. During development, this time decreases to 1 ms. There are two reasons for this drastic decrease. First, the inward current becomes primarily carried by sodium channels.[10] Second, the delayed rectifier, a potassium channel current, increases to 3.5 times its initial strength.[9]

text: In order for the transition from a calcium-dependent action potential to a sodium-dependent action potential to proceed new channels must be added to the membrane. If Xenopus neurons are grown in an environment with RNA synthesis or protein synthesis inhibitors that transition is prevented.[11] Even the electrical activity of the cell itself may play a role in channel expression. If action potentials in Xenopus myocytes are blocked, the typical increase in sodium and potassium current density is prevented or delayed.[12]

text: This maturation of electrical properties is seen across species. Xenopus sodium and potassium currents increase drastically after a neuron goes through its final phase of mitosis. The sodium current density of rat cortical neurons increases by 600% within the first two postnatal weeks.[9]

text: Neurotransmission[edit]

text: Anatomy of a neuron[edit]

text:
Structure of a typical neuron

Neuron

Dendrite
Soma
Axon
Nucleus
Node of
Ranvier
Axon terminal
Schwann cell
Myelin sheath

text: Several types of cells support an action potential, such as plant cells, muscle cells, and the specialized cells of the heart (in which occurs the cardiac action potential). However, the main excitable cell is the neuron, which also has the simplest mechanism for the action potential.

text: Neurons are electrically excitable cells composed, in general, of one or more dendrites, a single soma, a single axon and one or more axon terminals. Dendrites are cellular projections whose primary function is to receive synaptic signals. Their protrusions, known as dendritic spines, are designed to capture the neurotransmitters released by the presynaptic neuron. They have a high concentration of ligand-gated ion channels. These spines have a thin neck connecting a bulbous protrusion to the dendrite. This ensures that changes occurring inside the spine are less likely to affect the neighboring spines. The dendritic spine can, with rare exception (see LTP), act as an independent unit. The dendrites extend from the soma, which houses the nucleus, and many of the "normal" eukaryotic organelles. Unlike the spines, the surface of the soma is populated by voltage activated ion channels. These channels help transmit the signals generated by the dendrites. Emerging out from the soma is the axon hillock. This region is characterized by having a very high concentration of voltage-activated sodium channels. In general, it is considered to be the spike initiation zone for action potentials,[13] i.e. the trigger zone. Multiple signals generated at the spines, and transmitted by the soma all converge here. Immediately after the axon hillock is the axon. This is a thin tubular protrusion traveling away from the soma. The axon is insulated by a myelin sheath. Myelin is composed of either Schwann cells (in the peripheral nervous system) or oligodendrocytes (in the central nervous system), both of which are types of glial cells. Although glial cells are not involved with the transmission of electrical signals, they communicate and provide important biochemical support to neurons.[14] To be specific, myelin wraps multiple times around the axonal segment, forming a thick fatty layer that prevents ions from entering or escaping the axon. This insulation prevents significant signal decay as well as ensuring faster signal speed. This insulation, however, has the restriction that no channels can be present on the surface of the axon. There are, therefore, regularly spaced patches of membrane, which have no insulation. These nodes of Ranvier can be considered to be "mini axon hillocks", as their purpose is to boost the signal in order to prevent significant signal decay. At the furthest end, the axon loses its insulation and begins to branch into several axon terminals. These presynaptic terminals, or synaptic boutons, are a specialized area within the axon of the presynaptic cell that contains neurotransmitters enclosed in small membrane-bound spheres called synaptic vesicles.

text: Initiation[edit]

text: Before considering the propagation of action potentials along axons and their termination at the synaptic knobs, it is helpful to consider the methods by which action potentials can be initiated at the axon hillock. The basic requirement is that the membrane voltage at the hillock be raised above the threshold for firing.[3][4][15][16] There are several ways in which this depolarization can occur.

text: Dynamics[edit]

text: Action potentials are most commonly initiated by excitatory postsynaptic potentials from a presynaptic neuron.[17] Typically, neurotransmitter molecules are released by the presynaptic neuron. These neurotransmitters then bind to receptors on the postsynaptic cell. This binding opens various types of ion channels. This opening has the further effect of changing the local permeability of the cell membrane and, thus, the membrane potential. If the binding increases the voltage (depolarizes the membrane), the synapse is excitatory. If, however, the binding decreases the voltage (hyperpolarizes the membrane), it is inhibitory. Whether the voltage is increased or decreased, the change propagates passively to nearby regions of the membrane (as described by the cable equation and its refinements). Typically, the voltage stimulus decays exponentially with the distance from the synapse and with time from the binding of the neurotransmitter. Some fraction of an excitatory voltage may reach the axon hillock and may (in rare cases) depolarize the membrane enough to provoke a new action potential. More typically, the excitatory potentials from several synapses must work together at nearly the same time to provoke a new action potential. Their joint efforts can be thwarted, however, by the counteracting inhibitory postsynaptic potentials.

text: Neurotransmission can also occur through electrical synapses.[18] Due to the direct connection between excitable cells in the form of gap junctions, an action potential can be transmitted directly from one cell to the next in either direction. The free flow of ions between cells enables rapid non-chemical-mediated transmission. Rectifying channels ensure that action potentials move only in one direction through an electrical synapse.[citation needed] Electrical synapses are found in all nervous systems, including the human brain, although they are a distinct minority.[19]

text: "All-or-none" principle[edit]

text: The amplitude of an action potential is independent of the amount of current that produced it. In other words, larger currents do not create larger action potentials. Therefore, action potentials are said to be all-or-none signals, since either they occur fully or they do not occur at all.[d][e][f] This is in contrast to receptor potentials, whose amplitudes are dependent on the intensity of a stimulus.[20] In both cases, the frequency of action potentials is correlated with the intensity of a stimulus.

text: Sensory neurons[edit]

text: In sensory neurons, an external signal such as pressure, temperature, light, or sound is coupled with the opening and closing of ion channels, which in turn alter the ionic permeabilities of the membrane and its voltage.[21] These voltage changes can again be excitatory (depolarizing) or inhibitory (hyperpolarizing) and, in some sensory neurons, their combined effects can depolarize the axon hillock enough to provoke action potentials. Some examples in humans include the olfactory receptor neuron and Meissner's corpuscle, which are critical for the sense of smell and touch, respectively. However, not all sensory neurons convert their external signals into action potentials; some do not even have an axon![22] Instead, they may convert the signal into the release of a neurotransmitter, or into continuous graded potentials, either of which may stimulate subsequent neuron(s) into firing an action potential. For illustration, in the human ear, hair cells convert the incoming sound into the opening and closing of mechanically gated ion channels, which may cause neurotransmitter molecules to be released. In similar manner, in the human retina, the initial photoreceptor cells and the next layer of cells (comprising bipolar cells and horizontal cells) do not produce action potentials; only some amacrine cells and the third layer, the ganglion cells, produce action potentials, which then travel up the optic nerve.

text: Pacemaker potentials[edit]

text: In sensory neurons, action potentials result from an external stimulus. However, some excitable cells require no such stimulus to fire: They spontaneously depolarize their axon hillock and fire action potentials at a regular rate, like an internal clock.[23] The voltage traces of such cells are known as pacemaker potentials.[24] The cardiac pacemaker cells of the sinoatrial node in the heart provide a good example.[g] Although such pacemaker potentials have a natural rhythm, it can be adjusted by external stimuli; for instance, heart rate can be altered by pharmaceuticals as well as signals from the sympathetic and parasympathetic nerves.[25] The external stimuli do not cause the cell's repetitive firing, but merely alter its timing.[24] In some cases, the regulation of frequency can be more complex, leading to patterns of action potentials, such as bursting.

text: Phases[edit]

text: The course of the action potential can be divided into five parts: the rising phase, the peak phase, the falling phase, the undershoot phase, and the refractory period. During the rising phase the membrane potential depolarizes (becomes more positive). The point at which depolarization stops is called the peak phase. At this stage, the membrane potential reaches a maximum. Subsequent to this, there is a falling phase. During this stage the membrane potential becomes more negative, returning towards resting potential. The undershoot, or afterhyperpolarization, phase is the period during which the membrane potential temporarily becomes more negatively charged than when at rest (hyperpolarized). Finally, the time during which a subsequent action potential is impossible or difficult to fire is called the refractory period, which may overlap with the other phases.[26]

text: The course of the action potential is determined by two coupled effects.[27] First, voltage-sensitive ion channels open and close in response to changes in the membrane voltage Vm. This changes the membrane's permeability to those ions.[28] Second, according to the Goldman equation, this change in permeability changes the equilibrium potential Em, and, thus, the membrane voltage Vm.[h] Thus, the membrane potential affects the permeability, which then further affects the membrane potential. This sets up the possibility for positive feedback, which is a key part of the rising phase of the action potential.[3][29] A complicating factor is that a single ion channel may have multiple internal "gates" that respond to changes in Vm in opposite ways, or at different rates.[30][i] For example, although raising Vm opens most gates in the voltage-sensitive sodium channel, it also closes the channel's "inactivation gate", albeit more slowly.[31] Hence, when Vm is raised suddenly, the sodium channels open initially, but then close due to the slower inactivation.

text: The voltages and currents of the action potential in all of its phases were modeled accurately by Alan Lloyd Hodgkin and Andrew Huxley in 1952,[i] for which they were awarded the Nobel Prize in Physiology or Medicine in 1963.[β] However, their model considers only two types of voltage-sensitive ion channels, and makes several assumptions about them, e.g., that their internal gates open and close independently of one another. In reality, there are many types of ion channels,[32] and they do not always open and close independently.[j]

text: Stimulation and rising phase[edit]

text: A typical action potential begins at the axon hillock[33] with a sufficiently strong depolarization, e.g., a stimulus that increases Vm. This depolarization is often caused by the injection of extra sodium cations into the cell; these cations can come from a wide variety of sources, such as chemical synapses, sensory neurons or pacemaker potentials.

text: For a neuron at rest, there is a high concentration of sodium and chloride ions in the extracellular fluid compared to the intracellular fluid while there is a high concentration of potassium ions in the intracellular fluid compared to the extracellular fluid. This concentration gradient along with potassium leak channels present on the membrane of the neuron causes an efflux of potassium ions making the resting potential close to EK ≈ –75 mV.[34] The depolarization opens both the sodium and potassium channels in the membrane, allowing the ions to flow into and out of the axon, respectively. If the depolarization is small (say, increasing Vm from −70 mV to −60 mV), the outward potassium current overwhelms the inward sodium current and the membrane repolarizes back to its normal resting potential around −70 mV.[3][4][5]However, if the depolarization is large enough, the inward sodium current increases more than the outward potassium current and a runaway condition (positive feedback) results: the more inward current there is, the more Vm increases, which in turn further increases the inward current.[3][29] A sufficiently strong depolarization (increase in Vm) causes the voltage-sensitive sodium channels to open; the increasing permeability to sodium drives Vm closer to the sodium equilibrium voltage ENa≈ +55 mV. The increasing voltage in turn causes even more sodium channels to open, which pushes Vm still further towards ENa. This positive feedback continues until the sodium channels are fully open and Vm is close to ENa.[3][4][35][36] The sharp rise in Vm and sodium permeability correspond to the rising phase of the action potential.[3][4][35][36]

text: The critical threshold voltage for this runaway condition is usually around −45 mV, but it depends on the recent activity of the axon. A membrane that has just fired an action potential cannot fire another one immediately, since the ion channels have not returned to the deactivated state. The period during which no new action potential can be fired is called the absolute refractory period.[37][38][39] At longer times, after some but not all of the ion channels have recovered, the axon can be stimulated to produce another action potential, but with a higher threshold, requiring a much stronger depolarization, e.g., to −30 mV. The period during which action potentials are unusually difficult to evoke is called the relative refractory period.[37][38][39]

text: Peak and falling phase[edit]

text: The positive feedback of the rising phase slows and comes to a halt as the sodium ion channels become maximally open. At the peak of the action potential, the sodium permeability is maximized and the membrane voltage Vm is nearly equal to the sodium equilibrium voltage ENa. However, the same raised voltage that opened the sodium channels initially also slowly shuts them off, by closing their pores; the sodium channels become inactivated.[31] This lowers the membrane's permeability to sodium relative to potassium, driving the membrane voltage back towards the resting value. At the same time, the raised voltage opens voltage-sensitive potassium channels; the increase in the membrane's potassium permeability drives Vm towards EK.[31] Combined, these changes in sodium and potassium permeability cause Vm to drop quickly, repolarizing the membrane and producing the "falling phase" of the action potential.[37][40][36][41]

text: Afterhyperpolarization[edit]

text: The raised voltage opened many more potassium channels than usual, and some of these do not close right away when the membrane returns to its normal resting voltage. In addition, further potassium channels open in response to the influx of calcium ions during the action potential. The potassium permeability of the membrane is transiently unusually high, driving the membrane voltage Vm even closer to the potassium equilibrium voltage EK. Hence, there is an undershoot or hyperpolarization, termed an afterhyperpolarization in technical language, that persists until the membrane potassium permeability returns to its usual value.[42][40]

text: Refractory period[edit]

text: Each action potential is followed by a refractory period, which can be divided into an absolute refractory period, during which it is impossible to evoke another action potential, and then a relative refractory period, during which a stronger-than-usual stimulus is required.[37][38][39] These two refractory periods are caused by changes in the state of sodium and potassium channel molecules. When closing after an action potential, sodium channels enter an "inactivated" state, in which they cannot be made to open regardless of the membrane potential—this gives rise to the absolute refractory period. Even after a sufficient number of sodium channels have transitioned back to their resting state, it frequently happens that a fraction of potassium channels remains open, making it difficult for the membrane potential to depolarize, and thereby giving rise to the relative refractory period. Because the density and subtypes of potassium channels may differ greatly between different types of neurons, the duration of the relative refractory period is highly variable.

text: The absolute refractory period is largely responsible for the unidirectional propagation of action potentials along axons.[43] At any given moment, the patch of axon behind the actively spiking part is refractory, but the patch in front, not having been activated recently, is capable of being stimulated by the depolarization from the action potential.

text: Propagation[edit]

text: The action potential generated at the axon hillock propagates as a wave along the axon.[44] The currents flowing inwards at a point on the axon during an action potential spread out along the axon, and depolarize the adjacent sections of its membrane. If sufficiently strong, this depolarization provokes a similar action potential at the neighboring membrane patches. This basic mechanism was demonstrated by Alan Lloyd Hodgkin in 1937. After crushing or cooling nerve segments and thus blocking the action potentials, he showed that an action potential arriving on one side of the block could provoke another action potential on the other, provided that the blocked segment was sufficiently short.[k]

text: Once an action potential has occurred at a patch of membrane, the membrane patch needs time to recover before it can fire again. At the molecular level, this absolute refractory period corresponds to the time required for the voltage-activated sodium channels to recover from inactivation, i.e., to return to their closed state.[38] There are many types of voltage-activated potassium channels in neurons, some of them inactivate fast (A-type currents) and some of them inactivate slowly or not inactivate at all; this variability guarantees that there will be always an available source of current for repolarization, even if some of the potassium channels are inactivated because of preceding depolarization. On the other hand, all neuronal voltage-activated sodium channels inactivate within several millisecond during strong depolarization, thus making following depolarization impossible until a substantial fraction of sodium channels have returned to their closed state. Although it limits the frequency of firing,[45] the absolute refractory period ensures that the action potential moves in only one direction along an axon.[43] The currents flowing in due to an action potential spread out in both directions along the axon.[46] However, only the unfired part of the axon can respond with an action potential; the part that has just fired is unresponsive until the action potential is safely out of range and cannot restimulate that part. In the usual orthodromic conduction, the action potential propagates from the axon hillock towards the synaptic knobs (the axonal termini); propagation in the opposite direction—known as antidromic conduction—is very rare.[47] However, if a laboratory axon is stimulated in its middle, both halves of the axon are "fresh", i.e., unfired; then two action potentials will be generated, one traveling towards the axon hillock and the other traveling towards the synaptic knobs.

text: Myelin and saltatory conduction[edit]

text: In order to enable fast and efficient transduction of electrical signals in the nervous system, certain neuronal axons are covered with myelin sheaths. Myelin is a multilamellar membrane that enwraps the axon in segments separated by intervals known as nodes of Ranvier. It is produced by specialized cells: Schwann cells exclusively in the peripheral nervous system, and oligodendrocytes exclusively in the central nervous system. Myelin sheath reduces membrane capacitance and increases membrane resistance in the inter-node intervals, thus allowing a fast, saltatory movement of action potentials from node to node.[l][m][n] Myelination is found mainly in vertebrates, but an analogous system has been discovered in a few invertebrates, such as some species of shrimp.[o] Not all neurons in vertebrates are myelinated; for example, axons of the neurons comprising the autonomous nervous system are not, in general, myelinated.

text: Myelin prevents ions from entering or leaving the axon along myelinated segments. As a general rule, myelination increases the conduction velocity of action potentials and makes them more energy-efficient. Whether saltatory or not, the mean conduction velocity of an action potential ranges from 1 meter per second (m/s) to over 100 m/s, and, in general, increases with axonal diameter.[p]

text: Action potentials cannot propagate through the membrane in myelinated segments of the axon. However, the current is carried by the cytoplasm, which is sufficient to depolarize the first or second subsequent node of Ranvier. Instead, the ionic current from an action potential at one node of Ranvier provokes another action potential at the next node; this apparent "hopping" of the action potential from node to node is known as saltatory conduction. Although the mechanism of saltatory conduction was suggested in 1925 by Ralph Lillie,[q] the first experimental evidence for saltatory conduction came from Ichiji Tasaki[r] and Taiji Takeuchi[s][48] and from Andrew Huxley and Robert Stämpfli.[t] By contrast, in unmyelinated axons, the action potential provokes another in the membrane immediately adjacent, and moves continuously down the axon like a wave.

text: Myelin has two important advantages: fast conduction speed and energy efficiency. For axons larger than a minimum diameter (roughly 1 micrometre), myelination increases the conduction velocity of an action potential, typically tenfold.[v] Conversely, for a given conduction velocity, myelinated fibers are smaller than their unmyelinated counterparts. For example, action potentials move at roughly the same speed (25 m/s) in a myelinated frog axon and an unmyelinated squid giant axon, but the frog axon has a roughly 30-fold smaller diameter and 1000-fold smaller cross-sectional area. Also, since the ionic currents are confined to the nodes of Ranvier, far fewer ions "leak" across the membrane, saving metabolic energy. This saving is a significant selective advantage, since the human nervous system uses approximately 20% of the body's metabolic energy.[v]

text: The length of axons' myelinated segments is important to the success of saltatory conduction. They should be as long as possible to maximize the speed of conduction, but not so long that the arriving signal is too weak to provoke an action potential at the next node of Ranvier. In nature, myelinated segments are generally long enough for the passively propagated signal to travel for at least two nodes while retaining enough amplitude to fire an action potential at the second or third node. Thus, the safety factor of saltatory conduction is high, allowing transmission to bypass nodes in case of injury. However, action potentials may end prematurely in certain places where the safety factor is low, even in unmyelinated neurons; a common example is the branch point of an axon, where it divides into two axons.[50]

text: Some diseases degrade myelin and impair saltatory conduction, reducing the conduction velocity of action potentials.[w] The most well-known of these is multiple sclerosis, in which the breakdown of myelin impairs coordinated movement.[51]

text: Cable theory[edit]

text: The flow of currents within an axon can be described quantitatively by cable theory[52] and its elaborations, such as the compartmental model.[53] Cable theory was developed in 1855 by Lord Kelvin to model the transatlantic telegraph cable[x] and was shown to be relevant to neurons by Hodgkin and Rushton in 1946.[y] In simple cable theory, the neuron is treated as an electrically passive, perfectly cylindrical transmission cable, which can be described by a partial differential equation[52]

text: where V(x, t) is the voltage across the membrane at a time t and a position x along the length of the neuron, and where λ and τ are the characteristic length and time scales on which those voltages decay in response to a stimulus. Referring to the circuit diagram on the right, these scales can be determined from the resistances and capacitances per unit length.[54]

text: These time and length-scales can be used to understand the dependence of the conduction velocity on the diameter of the neuron in unmyelinated fibers. For example, the time-scale τ increases with both the membrane resistance rm and capacitance cm. As the capacitance increases, more charge must be transferred to produce a given transmembrane voltage (by the equation Q = CV); as the resistance increases, less charge is transferred per unit time, making the equilibration slower. In similar manner, if the internal resistance per unit length ri is lower in one axon than in another (e.g., because the radius of the former is larger), the spatial decay length λ becomes longer and the conduction velocity of an action potential should increase. If the transmembrane resistance rm is increased, that lowers the average "leakage" current across the membrane, likewise causing λ to become longer, increasing the conduction velocity.

text: Termination[edit]

text: Chemical synapses[edit]

text: In general, action potentials that reach the synaptic knobs cause a neurotransmitter to be released into the synaptic cleft.[z] Neurotransmitters are small molecules that may open ion channels in the postsynaptic cell; most axons have the same neurotransmitter at all of their termini. The arrival of the action potential opens voltage-sensitive calcium channels in the presynaptic membrane; the influx of calcium causes vesicles filled with neurotransmitter to migrate to the cell's surface and release their contents into the synaptic cleft.[aa] This complex process is inhibited by the neurotoxins tetanospasmin and botulinum toxin, which are responsible for tetanus and botulism, respectively.[ab]

text: Electrical synapses[edit]

text: Some synapses dispense with the "middleman" of the neurotransmitter, and connect the presynaptic and postsynaptic cells together.[ac] When an action potential reaches such a synapse, the ionic currents flowing into the presynaptic cell can cross the barrier of the two cell membranes and enter the postsynaptic cell through pores known as connexons.[ad] Thus, the ionic currents of the presynaptic action potential can directly stimulate the postsynaptic cell. Electrical synapses allow for faster transmission because they do not require the slow diffusion of neurotransmitters across the synaptic cleft. Hence, electrical synapses are used whenever fast response and coordination of timing are crucial, as in escape reflexes, the retina of vertebrates, and the heart.

text: Neuromuscular junctions[edit]

text: A special case of a chemical synapse is the neuromuscular junction, in which the axon of a motor neuron terminates on a muscle fiber.[ae] In such cases, the released neurotransmitter is acetylcholine, which binds to the acetylcholine receptor, an integral membrane protein in the membrane (the sarcolemma) of the muscle fiber.[af] However, the acetylcholine does not remain bound; rather, it dissociates and is hydrolyzed by the enzyme, acetylcholinesterase, located in the synapse. This enzyme quickly reduces the stimulus to the muscle, which allows the degree and timing of muscular contraction to be regulated delicately. Some poisons inactivate acetylcholinesterase to prevent this control, such as the nerve agents sarin and tabun,[ag] and the insecticides diazinon and malathion.[ah]

text: Other cell types[edit]

text: Cardiac action potentials[edit]

text: The cardiac action potential differs from the neuronal action potential by having an extended plateau, in which the membrane is held at a high voltage for a few hundred milliseconds prior to being repolarized by the potassium current as usual.[ai] This plateau is due to the action of slower calcium channels opening and holding the membrane voltage near their equilibrium potential even after the sodium channels have inactivated.

text: The cardiac action potential plays an important role in coordinating the contraction of the heart.[ai] The cardiac cells of the sinoatrial node provide the pacemaker potential that synchronizes the heart. The action potentials of those cells propagate to and through the atrioventricular node (AV node), which is normally the only conduction pathway between the atria and the ventricles. Action potentials from the AV node travel through the bundle of His and thence to the Purkinje fibers.[note 2] Conversely, anomalies in the cardiac action potential—whether due to a congenital mutation or injury—can lead to human pathologies, especially arrhythmias.[ai] Several anti-arrhythmia drugs act on the cardiac action potential, such as quinidine, lidocaine, beta blockers, and verapamil.[aj]

text: Muscular action potentials[edit]

text: The action potential in a normal skeletal muscle cell is similar to the action potential in neurons.[55] Action potentials result from the depolarization of the cell membrane (the sarcolemma), which opens voltage-sensitive sodium channels; these become inactivated and the membrane is repolarized through the outward current of potassium ions. The resting potential prior to the action potential is typically −90mV, somewhat more negative than typical neurons. The muscle action potential lasts roughly 2–4 ms, the absolute refractory period is roughly 1–3 ms, and the conduction velocity along the muscle is roughly 5 m/s. The action potential releases calcium ions that free up the tropomyosin and allow the muscle to contract. Muscle action potentials are provoked by the arrival of a pre-synaptic neuronal action potential at the neuromuscular junction, which is a common target for neurotoxins.[ag]

text: Plant action potentials[edit]

text: Plant and fungal cells [ak] are also electrically excitable. The fundamental difference to animal action potentials is that the depolarization in plant cells is not accomplished by an uptake of positive sodium ions, but by release of negative chloride ions.[al][am][an] Together with the following release of positive potassium ions, which is common to plant and animal action potentials, the action potential in plants infers, therefore, an osmotic loss of salt (KCl), whereas the animal action potential is osmotically neutral, when equal amounts of entering sodium and leaving potassium cancel each other osmotically. The interaction of electrical and osmotic relations in plant cells [ao] indicates an osmotic function of electrical excitability in the common, unicellular ancestors of plants and animals under changing salinity conditions, whereas the present function of rapid signal transmission is seen as a younger accomplishment of metazoan cells in a more stable osmotic environment.[56] It must be assumed that the familiar signalling function of action potentials in some vascular plants (e.g. Mimosa pudica) arose independently from that in metazoan excitable cells.

text: Taxonomic distribution and evolutionary advantages[edit]

text: Action potentials are found throughout multicellular organisms, including plants, invertebrates such as insects, and vertebrates such as reptiles and mammals.[ap] Sponges seem to be the main phylum of multicellular eukaryotes that does not transmit action potentials, although some studies have suggested that these organisms have a form of electrical signaling, too.[aq] The resting potential, as well as the size and duration of the action potential, have not varied much with evolution, although the conduction velocity does vary dramatically with axonal diameter and myelination.

text:
Comparison of action potentials (APs) from a representative cross-section of animals[57]

Animal
Cell type
Resting potential (mV)
AP increase (mV)
AP duration (ms)
Conduction speed (m/s)

Squid (Loligo)
Giant axon
−60
120
0.75
35

Earthworm (Lumbricus)
Median giant fiber
−70
100
1.0
30

Cockroach (Periplaneta)
Giant fiber
−70
80–104
0.4
10

Frog (Rana)
Sciatic nerve axon
−60 to −80
110–130
1.0
7–30

Cat (Felis)
Spinal motor neuron
−55 to −80
80–110
1–1.5
30–120

text: Given its conservation throughout evolution, the action potential seems to confer evolutionary advantages. One function of action potentials is rapid, long-range signaling within the organism; the conduction velocity can exceed 110 m/s, which is one-third the speed of sound. For comparison, a hormone molecule carried in the bloodstream moves at roughly 8 m/s in large arteries. Part of this function is the tight coordination of mechanical events, such as the contraction of the heart. A second function is the computation associated with its generation. Being an all-or-none signal that does not decay with transmission distance, the action potential has similar advantages to digital electronics. The integration of various dendritic signals at the axon hillock and its thresholding to form a complex train of action potentials is another form of computation, one that has been exploited biologically to form central pattern generators and mimicked in artificial neural networks.

text: Experimental methods[edit]

text: The study of action potentials has required the development of new experimental methods. The initial work, prior to 1955, was carried out primarily by Alan Lloyd Hodgkin and Andrew Fielding Huxley, who were, along John Carew Eccles, awarded the 1963 Nobel Prize in Physiology or Medicine for their contribution to the description of the ionic basis of nerve conduction. It focused on three goals: isolating signals from single neurons or axons, developing fast, sensitive electronics, and shrinking electrodes enough that the voltage inside a single cell could be recorded.

text: The first problem was solved by studying the giant axons found in the neurons of the squid (Loligo forbesii and Doryteuthis pealeii, at the time classified as Loligo pealeii).[ar] These axons are so large in diameter (roughly 1 mm, or 100-fold larger than a typical neuron) that they can be seen with the naked eye, making them easy to extract and manipulate.[i][as] However, they are not representative of all excitable cells, and numerous other systems with action potentials have been studied.

text: The second problem was addressed with the crucial development of the voltage clamp,[at] which permitted experimenters to study the ionic currents underlying an action potential in isolation, and eliminated a key source of electronic noise, the current IC associated with the capacitance C of the membrane.[59] Since the current equals C times the rate of change of the transmembrane voltage Vm, the solution was to design a circuit that kept Vm fixed (zero rate of change) regardless of the currents flowing across the membrane. Thus, the current required to keep Vm at a fixed value is a direct reflection of the current flowing through the membrane. Other electronic advances included the use of Faraday cages and electronics with high input impedance, so that the measurement itself did not affect the voltage being measured.[60]

text: The third problem, that of obtaining electrodes small enough to record voltages within a single axon without perturbing it, was solved in 1949 with the invention of the glass micropipette electrode,[au] which was quickly adopted by other researchers.[av][aw] Refinements of this method are able to produce electrode tips that are as fine as 100 Å (10 nm), which also confers high input impedance.[61] Action potentials may also be recorded with small metal electrodes placed just next to a neuron, with neurochips containing EOSFETs, or optically with dyes that are sensitive to Ca2+ or to voltage.[ax]

text: While glass micropipette electrodes measure the sum of the currents passing through many ion channels, studying the electrical properties of a single ion channel became possible in the 1970s with the development of the patch clamp by Erwin Neher and Bert Sakmann. For this discovery, they were awarded the Nobel Prize in Physiology or Medicine in 1991.[γ] Patch-clamping verified that ionic channels have discrete states of conductance, such as open, closed and inactivated.

text: Optical imaging technologies have been developed in recent years to measure action potentials, either via simultaneous multisite recordings or with ultra-spatial resolution. Using voltage-sensitive dyes, action potentials have been optically recorded from a tiny patch of cardiomyocyte membrane.[ay]

text: Neurotoxins[edit]

text: Several neurotoxins, both natural and synthetic, are designed to block the action potential. Tetrodotoxin from the pufferfish and saxitoxin from the Gonyaulax (the dinoflagellate genus responsible for "red tides") block action potentials by inhibiting the voltage-sensitive sodium channel;[az] similarly, dendrotoxin from the black mamba snake inhibits the voltage-sensitive potassium channel. Such inhibitors of ion channels serve an important research purpose, by allowing scientists to "turn off" specific channels at will, thus isolating the other channels' contributions; they can also be useful in purifying ion channels by affinity chromatography or in assaying their concentration. However, such inhibitors also make effective neurotoxins, and have been considered for use as chemical weapons. Neurotoxins aimed at the ion channels of insects have been effective insecticides; one example is the synthetic permethrin, which prolongs the activation of the sodium channels involved in action potentials. The ion channels of insects are sufficiently different from their human counterparts that there are few side effects in humans.

text: History[edit]

text: The role of electricity in the nervous systems of animals was first observed in dissected frogs by Luigi Galvani, who studied it from 1791 to 1797.[ba] Galvani's results stimulated Alessandro Volta to develop the Voltaic pile—the earliest-known electric battery—with which he studied animal electricity (such as electric eels) and the physiological responses to applied direct-current voltages.[bb]

text: Scientists of the 19th century studied the propagation of electrical signals in whole nerves (i.e., bundles of neurons) and demonstrated that nervous tissue was made up of cells, instead of an interconnected network of tubes (a reticulum).[62] Carlo Matteucci followed up Galvani's studies and demonstrated that cell membranes had a voltage across them and could produce direct current. Matteucci's work inspired the German physiologist, Emil du Bois-Reymond, who discovered the action potential in 1843.[citation needed] The conduction velocity of action potentials was first measured in 1850 by du Bois-Reymond's friend, Hermann von Helmholtz.[citation needed] To establish that nervous tissue is made up of discrete cells, the Spanish physician Santiago Ramón y Cajal and his students used a stain developed by Camillo Golgi to reveal the myriad shapes of neurons, which they rendered painstakingly. For their discoveries, Golgi and Ramón y Cajal were awarded the 1906 Nobel Prize in Physiology.[δ] Their work resolved a long-standing controversy in the neuroanatomy of the 19th century; Golgi himself had argued for the network model of the nervous system.

text: The 20th century was a significant era for electrophysiology. In 1902 and again in 1912, Julius Bernstein advanced the hypothesis that the action potential resulted from a change in the permeability of the axonal membrane to ions.[bc][63] Bernstein's hypothesis was confirmed by Ken Cole and Howard Curtis, who showed that membrane conductance increases during an action potential.[bd] In 1907, Louis Lapicque suggested that the action potential was generated as a threshold was crossed,[be] what would be later shown as a product of the dynamical systems of ionic conductances. In 1949, Alan Hodgkin and Bernard Katz refined Bernstein's hypothesis by considering that the axonal membrane might have different permeabilities to different ions; in particular, they demonstrated the crucial role of the sodium permeability for the action potential.[bf] They made the first actual recording of the electrical changes across the neuronal membrane that mediate the action potential.[ε] This line of research culminated in the five 1952 papers of Hodgkin, Katz and Andrew Huxley, in which they applied the voltage clamp technique to determine the dependence of the axonal membrane's permeabilities to sodium and potassium ions on voltage and time, from which they were able to reconstruct the action potential quantitatively.[i] Hodgkin and Huxley correlated the properties of their mathematical model with discrete ion channels that could exist in several different states, including "open", "closed", and "inactivated". Their hypotheses were confirmed in the mid-1970s and 1980s by Erwin Neher and Bert Sakmann, who developed the technique of patch clamping to examine the conductance states of individual ion channels.[bg] In the 21st century, researchers are beginning to understand the structural basis for these conductance states and for the selectivity of channels for their species of ion,[bh] through the atomic-resolution crystal structures,[bi] fluorescence distance measurements[bj] and cryo-electron microscopy studies.[bk]

text: Julius Bernstein was also the first to introduce the Nernst equation for resting potential across the membrane; this was generalized by David E. Goldman to the eponymous Goldman equation in 1943.[h] The sodium–potassium pump was identified in 1957[bl][ζ] and its properties gradually elucidated,[bm][bn][bo] culminating in the determination of its atomic-resolution structure by X-ray crystallography.[bp] The crystal structures of related ionic pumps have also been solved, giving a broader view of how these molecular machines work.[bq]

text: Quantitative models[edit]

text: Mathematical and computational models are essential for understanding the action potential, and offer predictions that may be tested against experimental data, providing a stringent test of a theory. The most important and accurate of the early neural models is the Hodgkin–Huxley model, which describes the action potential by a coupled set of four ordinary differential equations (ODEs).[i] Although the Hodgkin–Huxley model may be a simplification with few limitations[64] compared to the realistic nervous membrane as it exists in nature, its complexity has inspired several even-more-simplified models,[65][br] such as the Morris–Lecar model[bs] and the FitzHugh–Nagumo model,[bt] both of which have only two coupled ODEs. The properties of the Hodgkin–Huxley and FitzHugh–Nagumo models and their relatives, such as the Bonhoeffer–van der Pol model,[bu] have been well-studied within mathematics,[66][bv] computation[67] and electronics.[bw] However the simple models of generator potential and action potential fail to accurately reproduce the near threshold neural spike rate and spike shape, specifically for the mechanoreceptors like the Pacinian corpuscle.[68] More modern research has focused on larger and more integrated systems; by joining action-potential models with models of other parts of the nervous system (such as dendrites and synapses), researchers can study neural computation[69] and simple reflexes, such as escape reflexes and others controlled by central pattern generators.[70][bx]


document_title: Motorcycle club

question_text: what does mc mean on a biker vest

question_tokens: what does mc mean on a biker vest

root

text: Motorcycle club

text: Types of clubs, groups, and organizations[edit]

text: Most clubs are either organized around a brand or make, or around a type of riding (e.g. touring).[1] Motorcycle clubs vary a great deal in their objectives and organizations. Mainstream motorcycle clubs or associations typically have elected officers and directors, annual dues, and a regular publication. They may also sponsor sports events and annual or more frequent motorcycle rallies where members can socialize.

tag: p

text: There are a great many brand clubs, i.e. clubs dedicated to a particular marque, including those sponsored by various manufacturers, modeled on the original brand club, the Harley Owners Group. There are also large national independent motorcycle clubs, for example, the BMW Motorcycle Owners of America. There are also specific clubs for women, such as Women's International Motorcycle Association, and clubs for lesbians and gays, such as Dykes on Bikes.

text: Clubs catering for those interested in vintage machines such as the Vintage Motor Cycle Club are also popular as well as those centered on particular venues. Clubs catering for riders' rights such as the Motorcycle Action Group, and charities like The Royal British Legion Riders Branch are also popular. Many affiliate with an umbrella organization, such as the British Motorcyclists Federation in the UK, or FEMA in Europe. Producing national and local branch club magazines and events are typical activities of such clubs.

text: Other organizations whose activities primarily involve motorcycles exist for specific purposes or social causes such as the Patriot Guard Riders, who provide funeral escorts for military veterans, and Rolling Thunder, which advocates for troops missing in action and prisoners of war. While neither of the latter two groups require a motorcycle for membership, they are motorcycling-oriented and much of their activity involves rides.[2][3][4]

text: There are numerous religiously oriented clubs such as the Christian Motorcyclists Association, a biker ministry, charities such as Freewheelers EVS, which use motorcycles to provide an out-of-hours emergency medical courier service, and clubs which attract membership from specific groups, such as the Blue Knights Law Enforcement Motorcycle Club, for law enforcement personnel.[5]

text: History[edit]

text: One of the first motorcycle clubs was the New York Motorcycle Club, which in 1903 merged with the Alpha Motorcycle Club of Brooklyn to become the Federation of American Motorcyclists. Later, the Motorcycle and Allied Trades Association (M&ATA) formed a Rider Division which spun off into the American Motorcyclist Association.[6]

text: AMA[edit]

text: The American Motorcyclist Association (AMA) is the largest American motorcyclist organization. It serves as an umbrella organization for local clubs and sporting events. As of 2015, the AMA counts over 200,000 active members and over 1,200 chartered clubs.[7]

text: MCs and MCCs[edit]

text: The abbreviations MC and MCC are both used to mean "motorcycle club" but have a special social meaning from the point of view of the outlaw or one percenter motorcycling subculture. MC is generally reserved for those clubs that are mutually recognized by other MC or outlaw motorcycle clubs.[8] This is indicated by a motorcyclist wearing an MC patch, or a three-piece patch called colors, on the back of their jacket or riding vest. Outlaw or one percenter can mean merely that the club is not chartered under the auspices of the American Motorcyclist Association,[9] implying a radical rejection of authority and embracing of the "biker" lifestyle as defined and popularized since the 1950s and represented by such media as Easyriders magazine, the work of painter David Mann and others. In many contexts the terms overlap with the usual meaning of "outlaw" because some of these clubs, or some of their members, are recognized by law enforcement agencies as taking part in organized crime.

text: Outside of the outlaw motorcyclist subculture, the words "motorcycle club" carry no pejorative meaning beyond the everyday English definition of the words – a club involving motorcycles, whose members come from every walk of life. Thus, there are clubs that are culturally and stylistically nothing like outlaw or one percenter clubs, and whose activities and goals not similar to them at all, but still use three-part patches or the initials MC in their name or insignia.[10] In other countries, such motorcycle clubs will adopt the abbreviation MCC.


document_title: List of Los Angeles television stations

question_text: what channel is fox news in los angeles

question_tokens: what channel is fox news in los angeles

text: List of Los Angeles television stations

text: Los Angeles and surrounding cities are served by several local over-the-air television stations including:

text:
Call sign

Channel

Network

Virtual

RF

KCBS

2

43

CBS

KNBC

4

36

NBC

KTLA

5

31

The CW

KSFV

6

22

Ind

KABC

7

7

ABC

KFLA

8

8

Ind

KCAL

9

9

Ind

KIIO

10

10

Ind

KTTV

11

11

Fox

KCOP

13

13

MyNetworkTV

KSCI

18

18

Ind

KVME

20

20

Heroes & Icons

KNLA

20

32

Ind

KWHY

22

42

Ind

KVCR

24

26

PBS

KNET

25

50

HSN

KVHD

26

40

EVINE Live

KHTV

27

27

HSN

KCET

28

28

Ind

KPXN

30

38

Ion

KVMD

31

23

LATV

KMEX

34

34

Univision

KTAV-LD

35

46

Almavision

KHIZ-LD

39

2

Ind

KTBN

40

33

TBN

KXLA

44

51

Ind

KFTR

46

29

UniMás

KRVD

50

5

Ind

KOCE

50

18

PBS

KEDD

50

50

Ind

KVEA

52

39

Telemundo

KAZA

54

47

MeTV

KDOC

56

32

Ind

KJLA

57

49

Azteca

KLCS

58

41

PBS

KRCA

62

35

Estrella TV

KBEH

63

24

Ind

KILM

64

44

Punch TV

tag: table

text: Lists of television channels in the United States

tag: ul


document_title: List of Cleveland Browns seasons

question_text: when was the last time that the cleveland browns won a game

text: List of Cleveland Browns seasons

text: The Cleveland Browns were a charter member club of the All-America Football Conference (AAFC) when the league was founded in 1946. From 1946 to 1949, the Browns won each of the league's four championships. The National Football League (NFL) does not recognize the Browns' AAFC championships; however, the Pro Football Hall of Fame does recognize the team's championships, which is reflected in this list. When the AAFC folded in 1949, the Browns were absorbed into the NFL in 1950. The Browns went on to win three NFL championships, nearly dominating the NFL in the 1950s, and won one more NFL championship in 1964. The team has yet to appear in a Super Bowl, however. Overall, the team has won eight championships: four in the AAFC, and four in the NFL.

text: In 1996, then-Browns owner Art Modell made the decision to move the team from Cleveland, Ohio to Baltimore, Maryland. An agreement between the city of Cleveland and the NFL kept the team's history, name and colors in Cleveland, while Modell's new team would be regarded as an expansion team. The Baltimore Ravens would begin play in 1996, and the Browns would return to the league in 1999. For record-keeping purposes, the Browns are considered to have suspended operations from 1996 to 1998, which is reflected in this list. The Cleveland Browns are the second team in NFL History to reach an 0-16 record.

text: For a complete team history, see History of the Cleveland Browns.

text:
AAFC champions[1] (1946–1949)
NFL champions (1950–1969)
Super Bowl champions[2] (1970–present)
Conference champions
Division champions
Wild Card berth

text:
Season
Team
League
Conference
Division
Regular season results
Postseason results
Awards

Finish
Wins
Losses
Ties

All-America Football Conference

1946
1946
AAFC

Western
1st
12
2
0
Won AAFC championship (1) (Yankees) 14–9

1947
1947
AAFC

Western
1st
12
1
1
Won AAFC championship (2) (at Yankees) 14–3

1948
1948
AAFC

Western
1st
14
0
0
Won AAFC championship (3) (Bills) 49–7

1949
1949
AAFC

1st
9
1
2
Won AAFC playoff game (Bills) 31–21
Won AAFC championship (4) (49ers) 21–7
Paul Brown (COY)

National Football League (1950–1995; 1999–present)

1950
1950
NFL
American

T-1st[3]
10
2
0
Won Conference Playoffs (Giants) 8–3
Won NFL Championship (5) (Rams) 30–28

1951
1951
NFL
American

1st
11
1
0
Lost NFL Championship (at Rams) 17–24
Paul Brown (COY)
Otto Graham (MVP)

1952
1952
NFL
American

1st
8
4
0
Lost NFL Championship (Lions) 7–17

1953
1953
NFL
Eastern

1st
11
1
0
Lost NFL Championship (at Lions) 16–17
Paul Brown (COY)
Otto Graham (MVP)

1954
1954
NFL
Eastern

1st
9
3
0
Won NFL Championship (6) (Lions) 56–10

1955
1955
NFL
Eastern

1st
9
2
1
Won NFL Championship (7) (at Rams) 38–14
Otto Graham (MVP)

1956
1956
NFL
Eastern

T-4th[4]
5
7
0

1957
1957
NFL
Eastern

1st
9
2
1
Lost NFL Championship (at Lions) 14–59
Paul Brown (COY)
Jim Brown (MVP, ROY)

1958
1958
NFL
Eastern

T-1st[5]
9
3
0
Lost Conference Playoffs (at Giants) 0–10
Jim Brown (MVP)

1959
1959
NFL
Eastern

T-2nd[6]
7
5
0

1960
1960
NFL
Eastern

2nd
8
3
1

1961
1961
NFL
Eastern

3rd
8
5
1

1962
1962
NFL
Eastern

3rd
7
6
1

1963
1963
NFL
Eastern

2nd
10
4
0

Jim Brown (BBA, MVP)

1964
1964
NFL
Eastern

1st
10
3
1
Won NFL Championship (8)[7] (Colts) 27–0

1965
1965
NFL
Eastern

1st
11
3
0
Lost NFL Championship (at Packers) 12–23
Jim Brown (MVP, MVP)

1966
1966
NFL
Eastern

T-2nd[8]
9
5
0

1967
1967
NFL
Eastern
Century
1st
9
5
0
Lost Conference Championship (at Cowboys) 14–52

1968
1968
NFL
Eastern
Century
1st
10
4
0
Won Conference Championship (Cowboys) 31–20
Lost NFL Championship (Colts) 0–34
Leroy Kelly (MVP)

1969
1969
NFL
Eastern
Century
1st
10
3
1
Won Conference Championship (at Cowboys) 38–14
Lost NFL Championship (at Vikings) 7–27

1970
1970
NFL
AFC
Central
2nd
7
7
0

1971
1971
NFL
AFC
Central
1st
9
5
0
Lost Divisional Playoffs (Colts) 3–20

1972
1972
NFL
AFC
Central
2nd
10
4
0
Lost Divisional Playoffs (at Dolphins) 14–20

1973
1973
NFL
AFC
Central
3rd
7
5
2

1974
1974
NFL
AFC
Central
4th
4
10
0

1975
1975
NFL
AFC
Central
4th
3
11
0

1976
1976
NFL
AFC
Central
2nd
9
5
0

Forrest Gregg (COY)

1977
1977
NFL
AFC
Central
4th
6
8
0

1978[9]
1978
NFL
AFC
Central
3rd
8
8
0

1979
1979
NFL
AFC
Central
3rd
9
7
0

Sam Rutigliano (COY)

1980
1980
NFL
AFC
Central
1st
11
5
0
Lost Divisional Playoffs (Raiders) 12–14[10]
Sam Rutigliano (COY)
Brian Sipe (MVP, MVP, POY)

1981
1981
NFL
AFC
Central
4th
5
11
0

1982[11]
1982
NFL
AFC

8th
4
5
0
Lost First Round Playoffs (at Raiders) 10–27
Chip Banks (Def. ROY)

1983
1983
NFL
AFC
Central
2nd
9
7
0

1984
1984
NFL
AFC
Central
3rd
5
11
0

1985
1985
NFL
AFC
Central
1st
8
8
0
Lost Divisional Playoffs (at Dolphins) 21–24
Kevin Mack (ROY)

1986
1986
NFL
AFC
Central
1st
12
4
0
Won Divisional Playoffs (Jets 23–20) (2 OT)
Lost AFC Championship[12] (Broncos) 20–23 (OT)
Marty Schottenheimer (COY)

1987[13]
1987
NFL
AFC
Central
1st
10
5
0
Won Divisional Playoffs (Colts) 38–21
Lost AFC Championship[14] (at Broncos) 33–38

1988
1988
NFL
AFC
Central
2nd[15]
10
6
0
Lost Wild Card Playoffs (Oilers) 23–24

1989
1989
NFL
AFC
Central
1st
9
6
1
Won Divisional Playoffs (Bills) 34–30
Lost AFC Championship[16] (at Broncos) 21–37
Michael Dean Perry (Def. POY)

1990
1990
NFL
AFC
Central
4th
3
13
0

1991
1991
NFL
AFC
Central
3rd
6
10
0

1992
1992
NFL
AFC
Central
3rd
7
9
0

1993
1993
NFL
AFC
Central
3rd
7
9
0

1994
1994
NFL
AFC
Central
2nd
11
5
0
Won Wild Card Playoffs (Patriots) 20–13
Lost Divisional Playoffs (at Steelers) 9–29

1995
1995
NFL
AFC
Central
4th
5
11
0

1996
Inactive from 1996 to 1998

1997

1998

1999
1999
NFL
AFC
Central
6th
2
14
0

2000
2000
NFL
AFC
Central
6th
3
13
0

2001
2001
NFL
AFC
Central
3rd[17]
7
9
0

2002
2002
NFL
AFC
North
2nd
9
7
0
Lost Wild Card Playoffs (at Steelers) 33–36

2003
2003
NFL
AFC
North
4th
5
11
0

2004
2004
NFL
AFC
North
4th
4
12
0

2005
2005
NFL
AFC
North
4th[18]
6
10
0

2006
2006
NFL
AFC
North
4th
4
12
0

2007
2007
NFL
AFC
North
2nd[19]
10
6
0

2008
2008
NFL
AFC
North
4th
4
12
0

2009
2009
NFL
AFC
North
4th
5
11
0

2010
2010
NFL
AFC
North
3rd
5
11
0

2011
2011
NFL
AFC
North
4th
4
12
0

2012
2012
NFL
AFC
North
4th
5
11
0

2013
2013
NFL
AFC
North
4th
4
12
0

2014
2014
NFL
AFC
North
4th
7
9
0

2015
2015
NFL
AFC
North
4th
3
13
0

2016
2016
NFL
AFC
North
4th
1
15
0

2017
2017
NFL
AFC
North
4th
0
16
0

Totals
4 AAFC championships
4 NFL championships
12 conference titles
9 NFL division titles

47
4
3
All-America Football Conference regular season results[20]

5
0
0
AAFC postseason results

462
482
10
National Football League regular season results[20]

11
20
0
NFL postseason results[20]

525
506
13
AAFC and NFL regular and postseason results

text: Footnotes[edit]

text:
Jump up ^ The NFL does not recognize the Browns' AAFC championships. For the purposes of this list, however, they are included in final totals.
Jump up ^ The Browns are one of only four teams to have never appeared in a Super Bowl. The other three teams are the Detroit Lions, the Houston Texans, and the Jacksonville Jaguars.
Jump up ^ At the end of the 1950 NFL season, the Browns and Giants had identical 10–2–0 records. To determine the team that would play in the NFL Championship Game, the NFL held a one-game conference playoff. The Browns won, 8–3.
Jump up ^ At the end of the 1956 season, the Browns and the Steelers ended the season with identical 5–7 records. There were no tie-breaking procedures, so the teams ended the season tied.
Jump up ^ At the end of the 1958 NFL season, the Browns and Giants had identical 9–3–0 records. To determine the team that would play in the NFL Championship Game, the NFL held a one-game conference playoff. The Giants shut the Browns out 10–0.
Jump up ^ At the end of the 1959 season, the Browns and the Eagles ended the season with identical 5–7 records. There were no tie-breaking procedures, so the teams ended the season tied.
Jump up ^ The Browns' championship win in 1964 is the second most recent championship won by any sports team from the Cleveland area. The most recent being the Cleveland Cavaliers Championship win over the Golden State Warriors in 2016.
Jump up ^ At the end of the 1966 season, the Browns and the Eagles ended the season with identical 9–5 records. There were no tie-breaking procedures, so the teams ended the season tied.
Jump up ^ For the 1978 season, the NFL expanded from a 14-game season to a 16-game season.
Jump up ^ This game involved the play Red Right 88 in its final minutes.
Jump up ^ The 1982 NFL season was shortened from 16 games per team to 9 games because of a players' strike. The NFL adopted a special 16-team playoff tournament; eight teams from each conference were seeded 1–8, and division standings were ignored.
Jump up ^ The 1987 Conference Championship game between the Browns and the Broncos is best remembered for The Drive, in which quarterback John Elway, over the span of 5 minutes and 2 seconds, lead the Broncos on a 98-yard drive to tie the game with 37 seconds remaining in regulation. The Broncos won the game in overtime with a field goal, 23–20.
Jump up ^ The 1987 NFL season was shortened from 16 games per team to 15 games because of a players' strike. Games to be played during the third week of the season were canceled, and replacement players were used to play games from weeks 4 through 6.
Jump up ^ The 1988 Conference Championship game between the Browns and the Broncos is best remembered for The Fumble, in which, while on a potentially game-winning drive, the Browns' running back Ernest Byner fumbled the ball at the Broncos 3-yard line with 65 seconds remaining on the clock. The Broncos recovered the ball, allowed the Browns to get an intentional safety, and won the game, 38–33.
Jump up ^ At the end of the 1988 season, the Browns and the Oilers ended the season with identical 10–6 records. Using the NFL's tie-breaking procedures, Cleveland finished ahead of Houston based on a better division record.
Jump up ^ The 1990 Conference Championship game between the Browns and the Broncos marked the third time in four years that John Elway defeated Bernie Kosar and the Browns in the AFC championship game.
Jump up ^ At the end of the 2001 season, the Browns and the Titans ended the season with identical 7–9 records. Using the NFL's tie-breaking procedures, Cleveland finished ahead of Tennessee based on a better division record.
Jump up ^ At the end of the 2005 season, the Browns and the Ravens ended the season with identical 6–10 records. Using the NFL's tie-breaking procedures, Baltimore finished ahead of Cleveland based on a better division record.
Jump up ^ At the end of the 2007 season, the Browns and the Pittsburgh Steelers ended the season with identical 10–6 records. Using the NFL's tie-breaking procedures, the Steelers finished ahead of the Browns based on winning both games against the Browns during the season.
^ Jump up to: a b c "Cleveland Browns Team Encyclopedia - Pro-Football-Reference.com". pro-football-reference.com. Retrieved 14 January 2017.

tag: ol


document_title: McGruff the Crime Dog

question_text: who does the voice of mcgruff the dog

question_tokens: who does the voice of mcgruff the dog

text: McGruff the Crime Dog

text: History[edit]

text: Crime as a public concern[edit]

text: The decades prior to McGruff's creation saw an increase in U.S. public concern over crime. In the 1960s, a number of riots broke out across the U.S. and numerous public figures were assassinated, including President Kennedy, Martin Luther King, Jr., and Malcolm X.[1] Accepting the Republican nomination for president, Barry Goldwater positioned crime as one of the biggest issues facing the nation. While Goldwater lost to Lyndon Johnson, the issue of crime did not stop there. In July 1965, President Johnson formed the President's Commission on Law Enforcement and Administration of Justice to "probe ... fully and deeply into the problems of crime in our nation."[2][a]

text: After two years and $2.5 million, the Commission delivered its report, The Challenge of Crime in a Free Society, in February 1967 which influenced the Safe Streets and Control Act of 1968. The act gave $300 million to local police forces for more personnel and equipment.[7] With the election of Richard Nixon in 1968, the attempts to control rising crime rates shifted from a social approach—the "War on Poverty"—to a tough on crime approach—the "War on Crime". Despite Nixon's attempts, crime continued to rise from 363.5 crimes per 100,000 people in 1970 to 549.5 in 1979. The Carter administration took the focus away from crime and onto nuclear arms control and human rights. During Carter's presidency, crime continued to be a concern with the "kill for thrill murders" of 1979, when two men killed four people over eight days in Western Pennsylvania.[8]

text: Creation[edit]

text: The Ad Council was first approached by the Department of Justice in 1977 to create a public campaign to engage the public in reducing crime. The FBI director recommended a campaign playing on fears to convince citizens to take personal safety steps, but the Ad Council rejected their proposal believing it would largely be ignored by an already frightened public. However, the Ad Council was still interested in a crime prevention campaign. Leo Perlis, a member of the Ad Council's Public Policy Committee, heard the proposal and liked the idea. He met with FBI Director Clarence M. Kelley, the head of the National Council on Crime and Delinquency, and a board member of the National Sheriffs' Association to form a coalition to direct the ad campaign.[9]

text: The Ad Council gave the creative responsibilities to Dancer Fitzgerald Sample who they had previously worked with on the Keep America Beautiful campaign. On February 8, 1979, the Ad Council's board of directors held a meeting where they and public officials met to listen to data Dancer Fitzgerald Sample had compiled. Dancer Fitzgerald Sample had conducted focus groups in a number of cities to determine public perceptions on crime. The focus groups found that the public believed police should be the ones to prevent crime, but that they were unwilling to pay more in taxes to support more officers. They recommended a campaign which would "emphasize that individual actions can reduce crime" and "offer easily accessible opportunities for people to participate."[10]

text: The task was given to Jack Keil, executive vice president and creative director of Dancer Fitzgerald Sample. Keil, thinking of Smokey the Bear, came up with the idea of an animal mascot. After coming up with the slogan—"Take a bite out of crime"—he settled upon the idea of a dog. His first version was "a Snoopy look-alike wearing a Keystone Cop hat."[11] His creative team however did not believe the dog would be taken seriously. In response, he gave the team a day to come up with a new version.[11]

text: Five teams of two—a copywriter and an art director—produced proposals. The rejected proposals included a bulldog version of J. Edgar Hoover, a golden retriever, an "aggressive-looking deputy dog", and a "mongrel who became a wonder dog".[12] The proposal Keil selected, which would go on to become McGruff, was a talking dog in a raincoat produced by Sherry Nemmers and Ray Krivascy who "was tired...he had seen the world, and he had epitomized all the detectives we had seen from Raymond Chandler to Dashiell Hammett and even Columbo."[12]

text: While lauded by Keil, the U.S. Department of Justice was less enthused by the idea of a talking dog as the spokesman for crime prevention. By 1979, the Law Enforcement Assistance Administration (LEAA), created by President Johnson, was being criticized for its wastefulness prompting President Carter to shut down the program. The public safety outreach, part of the LEAA, was one of the few programs saved by Robert Diegelman who was tasked with dismantling the LEAA. Diegelman saw value in the public outreach effort and so sent monthly reports to his superiors in order to assuage their concerns. Despite this, Attorney General Benjamin Civilleti criticised the effort saying: "Why has the LEAA gotten into a campaign that is spending good money on a talking dog?"[13] Civilleti ordered the campaign be shut down, but the advertisements had already been distributed to the media and were set to run.[14]

text: In November 1979, the dog was introduced at a press Conference in New York City with his slogan "Take a bite out of crime." 8 months later in July 1980, a nationwide contest to name the dog was concluded. "McGruff the Crime Dog" was selected as the winner with "Shurlocked Homes" as the runner-up.[15] The winning name was submitted by Officer John Isbell of the New Orleans Police Department.[15]

text: Initial impact[edit]

text: McGruff was the first Ad Council campaign to be independently evaluated. Garrett O'Keefe of the University of Denver was given a grant of $900,000 by the Justice Department's National Institute of Justice in order to evaluate the campaign. O'Keefe found that "media response to the campaign was excellent. More than $100 million of [ad] time and space had been donated by mid-1981, making McGruff one of the most popular Ad Council campaigns."[16] As a result of the advertisements, over 1 million free booklets had been distributed, and another 250,000 were purchased from the Government Printing Office. The Army printed 300,000 booklets for their own programs as well.

text: By the end of 1981, over 50% of Americans had seen at least one McGruff advertisement with one third reporting they had seen the advertisements more than ten times. The dominant medium of exposure was television advertisements, comprising 78% of views, followed by posters and billboards at 14%, and newspapers at 8%.[17] While the demographics of exposure were notably diverse, there were some trends in who saw the ads more often than others. The ads were found to reach demographics prone to crime—men, youth, people with less stable residences, and those living in lower-working-class neighborhoods—slightly more often than those populations less prone to crime. Of those who had seen the advertisements, 88% were able to articulate what they were "trying to get across" with 28% pointing out the advertisements' goals of getting citizens to participate in crime prevention programs and reporting crime to the police.

text: O'Keefe also asked some questions related to public perception of McGruff. He found that only 3% disliked McGruff, most calling him "too cutesy", while 57% liked him for being "attention-getting, clever, different, or appealing to all ages."[18] 36% of respondents were neutral to McGruff. 8% said that they were annoyed by the commercials while 59% said that they were "pleased" by them.[18]

text: In order to assess the impact of the McGruff advertisements, O'Keefe surveyed adults in 1979 and in 1981, a year before and a year after the premiere of the first McGruff advertisement.[19] Of the forty personal security measures that McGruff advertisements recommended, only seven were explicitly mentioned in TV advertisements: locking doors, leaving outdoor lights on, putting indoor lights on timers, asking neighbors to watch your house, watching the neighborhood, reporting suspicious activity, and forming community groups to prevent crime. Of those seven, six saw a significant increase in usage by the public after seeing McGruff advertisements. The only activity not to see an increase was locking doors, despite the first McGruff spot specifically advocating this.[19] O'Keefe hypothesizes that this is due to a plateau effect, as 75% of respondents in 1979 already reported locking their doors; the only personal security measure not mentioned in a television advertisement to see a significant increase was getting a dog.[19]

text: Campaigns[edit]

text: McGruff first debuted in 1980 with television, newspaper, billboard, and radio advertisements. The Ad Council and the National Crime Prevention Council still use McGruff in national campaigns to raise awareness about crime and crime prevention strategies. About 1500 law enforcement agencies use McGruff costumes as part of their outreach efforts in communities. McGruff advertisements feature a "fulfillment strategy", a means of contact for more information. Early advertisements contained PO Boxes that could be written to for more information, but now contain phone numbers and web sites.[20]

text: McGruff was well received in the 1980s, and current campaigns are similarly recognizable. In a survey done by Harris Interactive for the National Crime Prevention Council, McGruff was known by 9 in 10 adults, teens, and children once being prompted; about 3 in 4 adults, 8 in 10 teens, and 8 in 10 children recognized McGruff without being prompted. Respondents were asked how likely they were to take McGruff's advice. Children were found to be very receptive, with 8 in 10 responding they were likely to take his advice. 7 in 10 teens and 6 in 10 adults gave similar responses.[21]

text: Initial campaign[edit]

text: The first McGruff campaign featured three television and radio advertisements as well as billboards and posters. The campaign focused on raising awareness of the ability for citizens to help prevent crime through personal security steps, community awareness, and reporting crimes in progress.

text: The first television advertisement, "Stop a Crime", debuted in February 1980. The full 60 second advertisement features McGruff (voiced by Jack Keil) entering an unlocked house and telling the viewer, "All crime needs is a chance. Don't give it a chance" before giving tips on preventative measures.[22] These measure included locking doors, turning on exterior lights, securing windows, asking neighbors to watch the house during long absences, and putting lights on timers.[19][22]

text: The advertisement was followed by two more which focused on community crime prevention tactics: "The Gilstraps" and "Mimi Marth". In "The Gilstraps" McGruff is backgrounded by men loading furniture into a moving truck. McGruff points out that these are actually thieves stealing from the home of the titular Gilstraps. The camera cuts to the Gilstrap's neighbors who, knowing the Gilstraps are out of town, call the police.[23]

text: In order to show the effectiveness of community watch, McGruff creator Sherry Nemmers selected actual Hartford resident Mimi Marth for the advertisement which now bears her name. "Mimi Marth" shows Marth and another watch member, Albert Bell, responding to crimes in progress by reporting them to police on their radios. McGruff tells the viewer that "There's 126 of them, regular people like you and me, working against crime."[24]

text: Addressing kidnapping, drugs, and gun violence[edit]

text: The National Crime Prevention Council hired their first president and CEO, Jack Calhoun. Calhoun wanted to address the roots of crime saying, "At some point, I have to step out from my locked house and barred windows."[25] Calhoun reined in the use of McGruff in the National Crime Prevention Council's advertisements, believing that a cartoon in the serious contexts of abduction, drugs, and gun violence would be poorly received.

text: McGruff Houses and trucks[edit]

text: The McGruff House program was a program that designated temporary safe havens for children in emergency situations. The program was first created in Utah in 1982 in response to the kidnapping and murder of five children by Arthur Gary Bishop. Owners of houses and apartments, after clearing a background check, would display a sign in their window with the image of McGruff. Children would be educated at school and community events to go to these houses when they felt threatened or in need of help.[26]

text: The program operated under the motto "We'll call for help" and emphasized its use as a temporary haven.[26] Volunteers were trained to call the appropriate authorities in emergency situations and would provide emotional support to children in danger. The program made clear that volunteers were for emergency situations and even in such situations volunteers would not act as escorts or provide first aid "except in extreme emergency situations and then only if qualified."[27][28]

text: The first McGruff truck was established in Utah in 1986. A utility company asked that its trucks be designated as "rolling McGruff Houses" and were approved. The program was extended to other companies and municipalities, and in 2006 there were over 170 participants.[26] In February 2012, the McGruff House program was ended after nearly 30 years. The program was ended because, with the advent and growing prominence of cell phones, the need for McGruff Houses declined combined with tightening budgets.[29]

text: In 2018, the Martin Agency brought back McGruff as part of GEICO Insurance’s ‘surprising’ campaign. The TV spot has an animated McGruff attempting to share his investigation evidence with several human colleagues. They respond by not taking him seriously and treating him like an actual dog with 'baby talk', leading to McGruff throwing his paper work in the air and storming out of the scene.


document_title: Gram stain

question_text: what is the primary stain in the gram stain

text: Gram stain

text: History[edit]

text: The method is named after its inventor, the Danish scientist Hans Christian Gram (1853–1938), who developed the technique while working with Carl Friedländer in the morgue of the city hospital in Berlin in 1884. Gram devised his technique not for the purpose of distinguishing one type of bacterium from another but to make bacteria more visible in stained sections of lung tissue.[2] He published his method in 1884, and included in his short report the observation that the typhus bacillus did not retain the stain.[3]

text: Uses[edit]

text: Gram staining is a bacteriological laboratory technique[4] used to differentiate bacterial species into two large groups (gram-positive and gram-negative) based on the physical properties of their cell walls.[5][page needed] Gram staining is not used to classify archaea, formerly archaeabacteria, since these microorganisms yield widely varying responses that do not follow their phylogenetic groups.[6]

text: The Gram stain is not an infallible tool for diagnosis, identification, or phylogeny, and it is of extremely limited use in environmental microbiology. It is used mainly to make a preliminary morphologic identification or to establish that there are significant numbers of bacteria in a clinical specimen. It cannot identify bacteria to the species level, and for most medical conditions, it should not be used as the sole method of bacterial identification. In clinical microbiology laboratories, it is used in combination with other traditional and molecular techniques to identify bacteria. Some organisms are gram-variable (meaning they may stain either negative or positive); some are not stained with either dye used in the Gram technique and are not seen. In a modern environmental or molecular microbiology lab, most identification is done using genetic sequences and other molecular techniques, which are far more specific and informative than differential staining.

text: Gram staining has been suggested to be as effective a diagnostic tool as PCR in one primary research report regarding gonococcal urethritis.[7][non-primary source needed]

text: Medical[edit]

text: Gram stains are performed on body fluid or biopsy when infection is suspected. Gram stains yield results much more quickly than culturing, and is especially important when infection would make an important difference in the patient's treatment and prognosis; examples are cerebrospinal fluid for meningitis and synovial fluid for septic arthritis.[4][8]

text: Staining mechanism[edit]

text: Gram-positive bacteria have a thick mesh-like cell wall made of peptidoglycan (50–90% of cell envelope), and as a result are stained purple by crystal violet, whereas gram-negative bacteria have a thinner layer (10% of cell envelope), so do not retain the purple stain and are counter-stained pink by safranin. There are four basic steps of the Gram stain:

text:
Applying a primary stain (crystal violet) to a heat-fixed smear of a bacterial culture. Heat fixation kills some bacteria but is mostly used to affix the bacteria to the slide so that they don't rinse out during the staining procedure
The addition of iodide, which binds to crystal violet and traps it in the cell
Rapid decolorization with ethanol or acetone
Counterstaining with safranin.[9] Carbol fuchsin is sometimes substituted for safranin since it more intensely stains anaerobic bacteria, but it is less commonly used as a counterstain.[10]

text: Crystal violet (CV) dissociates in aqueous solutions into CV+ and chloride (Cl−) ions. These ions penetrate through the cell wall and cell membrane of both gram-positive and gram-negative cells. The CV+ ion interacts with negatively charged components of bacterial cells and stains the cells purple.[11]

text:
Iodide (I− or I−
3) interacts with CV+ and forms large complexes of crystal violet and iodine (CV–I) within the inner and outer layers of the cell. Iodine is often referred to as a mordant, but is a trapping agent that prevents the removal of the CV–I complex and, therefore, color the cell.[12]

text: When a decolorizer such as alcohol or acetone is added, it interacts with the lipids of the cell membrane.[13] A gram-negative cell loses its outer lipopolysaccharide membrane, and the inner peptidoglycan layer is left exposed. The CV–I complexes are washed from the gram-negative cell along with the outer membrane.[14][citation needed] In contrast, a gram-positive cell becomes dehydrated from an ethanol treatment. The large CV–I complexes become trapped within the gram-positive cell due to the multilayered nature of its peptidoglycan.[14][citation needed] The decolorization step is critical and must be timed correctly; the crystal violet stain is removed from both gram-positive and negative cells if the decolorizing agent is left on too long (a matter of seconds).[15][citation needed]

text: After decolorization, the gram-positive cell remains purple and the gram-negative cell loses its purple color.[15][citation needed] Counterstain, which is usually positively charged safranin or basic fuchsine, is applied last to give decolorized gram-negative bacteria a pink or red color.[16][17]

text: Examples[edit]

text: Gram-positive bacteria[edit]

text: Gram-positive bacteria generally have a single membrane (monoderm) surrounded by a thick peptidoglycan. This rule is followed by two phyla: Firmicutes (except for the classes Mollicutes and Negativicutes) and the Actinobacteria.[5][18] In contrast, members of the Chloroflexi (green non-sulfur bacteria) are monoderms but possess a thin or absent (class Dehalococcoidetes) peptidoglycan and can stain negative, positive or indeterminate; members of the Deinococcus-Thermus group, stain positive but are diderms with a thick peptidoglycan.[5][page needed] [18]

text: Historically, the gram-positive forms made up the phylum Firmicutes, a name now used for the largest group. It includes many well-known genera such as Bacillus, Listeria, Staphylococcus, Streptococcus, Enterococcus, and Clostridium.[19][citation needed] It has also been expanded to include the Mollicutes, bacteria like Mycoplasma that lack cell walls and so cannot be stained by Gram, but are derived from such forms.[20][citation needed]

text: Some bacteria have cell walls which are particularly adept at retaining stains. These will appear positive by Gram stain even though they are not closely related to other gram-positive bacteria. These are called acid fast bacteria, and can only be differentiated from other gram-positive bacteria by special staining procedures.[21][citation needed]

text: Gram-negative bacteria[edit]

text: Gram-negative bacteria generally possess a thin layer of peptidoglycan between two membranes (diderms). Most bacterial phyla are gram-negative, including the cyanobacteria, spirochaetes, and green sulfur bacteria, and most Proteobacteria (exceptions being some members of the Rickettsiales and the insect-endosymbionts of the Enterobacteriales).[5][page needed][18]

text: Gram variable and gram-indeterminate bacteria[edit]

text: Some bacteria, after staining with the Gram stain, yield a gram-variable pattern: a mix of pink and purple cells are seen.[14][citation needed] In cultures of Bacillus, Butyrivibrio, and Clostridium, a decrease in peptidoglycan thickness during growth coincides with an increase in the number of cells that stain gram-negative.[22] In addition, in all bacteria stained using the Gram stain, the age of the culture may influence the results of the stain.[23]

text: Gram-indeterminate bacteria do not respond predictably to Gram staining and, therefore, cannot be determined as either gram-positive or gram-negative. Examples include many species of Mycobacterium, including M. tuberculosis and M. leprae.[24][25]

text: Orthographic note[edit]

text: The term Gram staining is derived from the surname of Hans Christian Gram, the eponym (Gram) is therefore capitalized but not the common noun (stain) as is usual for scientific terms.[26] The adjectives 'gram-positive' and 'gram-negative'; as eponymous adjectives, their initial letter can be either lowercase 'g' or capital 'G', depending on whose style guide (if any) governs the document being written. Lowercase style is used by the US Centers for Disease Control and Prevention and other style regimens such as the AMA style.[27] Dictionaries may use lowercase,[28][29] uppercase,[30][31][32][33] or both.[34][35] Uppercase 'Gram-positive' or 'Gram-negative' usage is also common in many scientific journal articles and publications.[35][36][37] When articles are submitted to journals, each journal may or may not apply house style to the postprint version. Preprint versions contain whichever style the author happened to use. Even style regimens that use lowercase for the adjectives 'gram-positive' and 'gram-negative' still use capital for 'Gram stain'.