document_title: Action potential

question_text: the rising phase of the action potential is due to

question_tokens: the rising phase of the action potential is due to

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 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; that is, 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; some types, however, 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.[3] 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.

tag: ol

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 that are capable of producing the positive feedback necessary to generate an action potential 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.[4][5][6] 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.[4][7][8][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.[9] 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.[10] 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.[10]

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.[10] 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.[11] Second, the delayed rectifier, a potassium channel current, increases to 3.5 times its initial strength.[10]

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.[12] 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.[13]

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.[10]

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, or 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.[14] 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.[15] 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.[4][5][16][17] 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.[18] 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.[19] 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.[20]

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.[21] 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.[22] 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. 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![23] 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.[24] The voltage traces of such cells are known as pacemaker potentials.[25] 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.[26] The external stimuli do not cause the cell's repetitive firing, but merely alter its timing.[25] 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.[27]

text: The course of the action potential is determined by two coupled effects.[28] 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.[29] Second, according to the Goldman equation, this change in permeability changes in 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.[4][30] 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.[31][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.[32] 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,[33] 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[34] 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 chlorine 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.[35] 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.[4][5][6]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.[4][30] 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.[4][5][36][37] The sharp rise in Vm and sodium permeability correspond to the rising phase of the action potential.[4][5][36][37]

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.[38][39][40] 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.[38][39][40]

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.[32] 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.[32] 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.[38][41][37][42]

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.[43][41]

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.[38][39][40] 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.[44] 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.[45] 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.[39] 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,[46] the absolute refractory period ensures that the action potential moves in only one direction along an axon.[44] The currents flowing in due to an action potential spread out in both directions along the axon.[47] 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.[48] 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][49] 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.[51]

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.[52]

text: Cable theory[edit]

text: The flow of currents within an axon can be described quantitatively by cable theory[53] and its elaborations, such as the compartmental model.[54] 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[53]

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.[55]

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.[56] 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.[57] 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[58]

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.[60] 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.[61]

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.[62] 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 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).[63] 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 golden 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][64] 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[65] compared to the realistic nervous membrane as it exists in nature, its complexity has inspired several even-more-simplified models,[66][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,[67][bv] computation[68] 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.[69] 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[70] and simple reflexes, such as escape reflexes and others controlled by central pattern generators.[71][bx]


document_title: Ivor Novello

question_text: welsh actor who had theatre named after him

root

text: Ivor Novello

text: Early years[edit]

text: Novello was born in Cardiff, Wales, to David Davies (c. 1852–1931), a rent collector for the city council,[2] and his wife, Clara Novello Davies, an internationally known singing teacher and choral conductor.[3] As a boy, Novello was a successful singer in the Welsh Eisteddfod.[4] His mother set up as voice teacher in London, where he met leading performers, including members of George Edwardes's Gaiety Theatre company, classical musicians such as Landon Ronald, and singers such as Adelina Patti.[2] Another of his mother's associates was Clara Butt, who taught him to sing "Abide with Me" when he was a boy of six.[5]

tag: p

text: Novello was educated privately in Cardiff and then in Gloucester, where he studied harmony and counterpoint with Herbert Brewer, the cathedral organist.[6] From there he won a scholarship to Magdalen College School in Oxford, where he was a solo treble in the college choir. He later said that this prolonged youthful exposure to early sacred choral music had turned his tastes, in reaction, to lush romantic music.[2] Although Brewer had told him he would not have a career in music,[3] Novello from his early youth showed a facility for writing songs, and when he was only 15, one of his songs was published.[7] After leaving school, he gave piano lessons in Cardiff, and then moved to London in 1913 with his mother. They took a flat above the Strand Theatre, which became his London home for the rest of his life.[2][8]

text: In London he found a mentor in Sir Edward Marsh, a well-known patron of the arts. Marsh encouraged him to compose and introduced him to people who could help his career.[2] He adopted part of his mother's maiden name, "Novello" as his professional surname, although he did not change it legally until 1927.[9]

text:
Keep the Home Fires Burning

Performed by Frederick Wheeler for Edison Records in late 1915.

Problems playing this file? See media help.

tag: table

text: In 1914, at the start of the First World War, Novello wrote "Keep the Home Fires Burning", a song that expressed the feelings of innumerable families sundered by World War I. Novello composed the music for the song to a lyric by the American Lena Guilbert Ford, and it became a huge popular success, bringing Novello money and fame at the age of 21.[6][10] In other respects, the war had less impact on Novello than on many young men of his age. He avoided enlistment until June 1916, when he reported to a Royal Naval Air Service (RNAS) training depot as a probationary flight sub-lieutenant. After twice crashing an aeroplane, and with the influence of Marsh, he was moved to the Air Ministry office in central London performing clerical duties for the duration of the war.[11]

text: Composer and actor[edit]

text: Novello continued to write songs while serving in the RNAS. He had his first stage success with Theodore & Co in 1916, a production by George Grossmith, Jr. and Edward Laurillard with a score composed by Novello and the young Jerome Kern.[12] In the same year, Novello contributed to André Charlot's revue See-Saw.[2] In 1917 he wrote for another Grossmith and Laurillard production, the operette Arlette, for which he contributed additional numbers to an existing French score by Jane Vieu and Guy le Feuvre.[13] In the same year, Marsh introduced him to the actor Bobbie Andrews, who became Novello's life partner.[2] Andrews introduced Novello to the young Noël Coward. Coward, six years Novello's junior, was deeply envious of Novello's effortless glamour.[6] He wrote, "I just felt suddenly conscious of the long way I had to go before I could break into the magic atmosphere in which he moved and breathed with such nonchalance".[14]

text: In 1918 and after the war, Novello continued to write successfully for musical comedy and revue. The former included Who's Hooper? (1919), an adaptation of a Pinero play, with a book by Fred Thompson, lyrics by Clifford Grey, and music by Howard Talbot and Novello,[15] and The Golden Moth by Thompson and P.G. Wodehouse (1921), for which Novello provided the entire score.[16] For Charlot, he contributed numbers to the revues Tabs (1918), A to Z (1921) and Puppets (1924). For the second of these, his songs included one of his few well-known comedy numbers, "And her mother came too", with lyrics by Dion Titheradge, written for Jack Buchanan.[2]

text: At the same time as his successes as a composer, Novello was making a career as an actor. With "a classic profile that gained him matinee idol status amongst the film-going public",[17] he was sought out, on the strength of a publicity photograph, by the Swiss film director Louis Mercanton. Mercanton offered him a silent-film role as the romantic lead in The Call of the Blood (1920).[6] In the same year, he made another film for Mercanton, Miarka.[2] Novello made his first English film, Carnival, the following year.[2]

text: Novello made his stage debut in 1921 in Deburau by Sacha Guitry with Robert Loraine, Madge Titheradge and Bobbie Andrews,[18] and, among other stage engagements, in the next years he played Bingley in an adaptation of Pride and Prejudice with Ben Webster as Darcy and Mary Jerrold as Elizabeth, in a cast that included Ellen Terry, May Whitty and Joyce Carey.[19] At about this time, Novello had an affair with the writer Siegfried Sassoon; it was short lived, but in the words of Sassoon's biographer John Stuart Roberts, Novello "was a consummate flirt who collected lovers as he gathered lilacs."[20]

text: In 1923, Novello made his American movie debut in D. W. Griffith's The White Rose. The same year, he starred in "The Man Without Desire", among other British films.[21] He next co-wrote, produced and starred in the successful 1924 play The Rat.[22] The play was made into a film in 1925, which was so successful that two sequels followed in 1926 and 1928.[2] His dramatic roles in the West End included the title character in the first London production of Ferenc Molnár's Liliom (1926).[23]

text: Other films in which Novello starred included Alfred Hitchcock's The Lodger, where he played the sinister title character, and Downhill (both in 1927). The British film company Gainsborough Pictures offered Novello a lucrative contract, which enabled him to buy a country house in Littlewick Green, near Maidenhead.[2] He renamed the property Redroofs, and he entertained there famously and with little regard for convention. Cecil Beaton, noting the frequent homosexual excesses, coined the phrase, "the Ivor/Noel naughty set".[24] Coward had by now caught Novello up professionally, despite a joint disaster when Novello starred in Coward's play Sirocco in 1927, which was a débâcle, and closed within a month of opening.[25][26] In 1928 Novello starred in the silent adaptation of Coward's much more successful The Vortex, and made his last silent film, A South Sea Bubble.[2] During the late 1920s, Novello was the most popular male star in British films.[27]

text: Novello returned to composing for the lyric stage in 1929, writing eight numbers for the revue The House that Jack Built. In the same year, he presented his own play Symphony in Two Flats, which he took to New York the following year. It was followed by a successful Broadway production of his The Truth Game, which brought him to the attention of Hollywood studios. He accepted a contract to write for and appear in MGM films. He found little to do in Hollywood, however, beyond writing the dialogue for Tarzan the Ape Man.[28] Returning to London, he starred in the sound remake of The Lodger (1932).[2]

text: 1930s musicals[edit]

text: After beginning the 1930s with a series of non-musical plays, I Lived With You (1932), Fresh Fields, Proscenium, Sunshine Sisters, Flies in the Sun (all 1933) and Murder in Mayfair (1934), Novello returned to composition in 1935 with Glamorous Night, which was the first of a series of enormously popular musicals.[6] The Times considered that it was for these that Novello would be popularly remembered.[7] Paul Webb, in the Grove Dictionary of Music and Musicians, writes that Novello's show saved the fortunes of the Theatre Royal, Drury Lane:

text: Dominating the British musical theatre from the mid-1930s to the early 1950s, his shows were heavily influenced by the operettas that he had grown up with (he saw Die lustige Witwe 27 times), but had a highly individual style of their own. Blending musicals with opera, operetta and both modern and classical dance, these shows were considered something of an anachronism in their own time, but that was part of their appeal.

text: Another model was Coward's 1929 musical Bitter Sweet, which Novello called "a lovely, lovely thing … sheer joy from beginning to end". That, too, was an old-fashioned musical, "so full of regret … for a vanished kindly silly darling age."[29]

text: For all his four 1930s musicals, Novello wrote the book and music, Christopher Hassall wrote the lyrics, and the orchestrations were by Charles Prentice. Glamorous Night starred Novello and Mary Ellis, with a cast including Zena Dare, Olive Gilbert and Elizabeth Welch, and ran from 2 May 1935 to 18 July 1936, at Drury Lane and then the London Coliseum.[30] Careless Rapture ran from 11 September 1936 for 296 performances, with Novello, Dorothy Dickson and Zena Dare in the leading roles.[31] Crest of the Wave starred Novello, Dickson and Gilbert, and ran from 1 September 1937 for 203 performances.[3] The last of Novello's pre-war musicals was The Dancing Years, which starred Novello, Ellis and Gilbert, opened at Drury Lane, closed on the outbreak of the Second World War, and re-opened at the Adelphi Theatre, running for a combined total of 696 performances, closing on 8 July 1944.[32] This show was the closest Novello came to fulfilling his mother's early ambitions for him to write operas; he played an Austrian composer-conductor at the Wiener Hofoper.[3]

text: Second World War and last years[edit]

text: Novello presented only two new shows during the Second World War. Arc de Triomphe (1943), a musical vehicle for Mary Ellis, was only a modest success, but Perchance to Dream (1945) was immensely successful, running for 1,022 performances. In between the two shows, Novello had been in serious legal trouble and served four weeks in prison for misuse of petrol coupons, a serious offence under rationing laws in wartime Britain. An admiring fan had stolen the coupons from her employer, but the court found that Novello was also culpable.[33] The prison term, though short, came as a severe shock to Novello, both mentally and physically, and had serious lasting effects.[2] Not everybody was supportive; Coward's sympathy was limited: "He's been fighting like a steer to keep going as before the war and hasn't done a thing for the general effort",[34] but when Novello returned to The Dancing Years after his release, he received "a rapturous ovation" on his first entrance.[2]

text: Novello's last full-scale production in this style, King's Rhapsody (1949), was, in Webb's words, "a selfconsciously romantic counter-blast to the modern musical: crown princes, ballrooms, royal yachts, beautiful princesses and a full-scale coronation".[3] After the rigours of war, this escapist entertainment had strong box-office appeal, and ran for 841 performances.[35] The show starred Novello and the cast included Phyllis Dare, Zena Dare, Olive Gilbert and Bobbie Andrews. It was still running, at the Palace Theatre, when Novello's last show opened. This was Gay's the Word (1951). Novello had written no role for himself; the show starred the comedy actress Cicely Courtneidge and was a departure from his established pattern, balancing the contrasting styles of European operetta and post-war American musicals.[2] The Times commented that the show "cheerfully parodied the very Ruritanian romances to which he owed his most triumphant successes."[7]

text: Death and legacy[edit]

text: Novello died suddenly from a coronary thrombosis at the age of 58, a few hours after completing a performance in the run of King's Rhapsody.[7] He was cremated at the Golders Green Crematorium, and his ashes are buried beneath a lilac bush and marked with a plaque that reads "Ivor Novello 6th March 1951 'Till you are home once more'."[36] He left an estate worth £160,000[37] (£4.53 million when adjusted for inflation).

text: Only a few weeks before Novello's death, Coward had written of him: "Theatre – good, bad and indifferent – is the love of his life. For him, other human endeavours are mere shadows. … The reward of his work lies in the indisputable fact that whenever and wherever he appears the vast majority of the British public flock to see him."[5] Grove's Dictionary of Music and Musicians writes of Novello that he was "until the advent of Andrew Lloyd Webber, the 20th-century's most consistently successful composer of British musicals."[3]

text: The Ivor Novello Awards for songwriting, established in 1955 in Novello's memory, are awarded each year by the British Academy of Songwriters, Composers and Authors (BASCA) to British songwriters and composers as well as to an outstanding international music writer.[38] A scholarship in memory of Novello was established at the Royal Academy of Dramatic Art, and in 1952 a bronze bust of him by Clemence Dane was unveiled at Drury Lane. In St. Paul's, Covent Garden, known as the actors' church, a panel was installed to commemorate Novello, and in 1972, to mark the 21st anniversary of his death, a memorial stone was unveiled in St. Paul's Cathedral.[2]

text: In 1993, the centenary of Novello's birth was marked by several celebratory shows around the UK, including one at the Players Theatre in London.[17] In 2005, the Strand Theatre, above which Novello lived for many years, was renamed the Novello Theatre, with a plaque in his honour set at the entrance.[39] On 27 June 2009, a statue of Novello was unveiled outside the Wales Millennium Centre in Cardiff Bay. Plaques detailing some of his best-known songs are fitted to the pedestal, along with a dedication to Novello.[40] Novello's memory is promoted by The Ivor Novello Appreciation Bureau, which holds annual events around Britain, including an annual pilgrimage to Redroofs each June. Redroofs was sold after Novello's death and is now a theatre training school.[41]

text: Novello was portrayed in Robert Altman's 2001 film, Gosford Park, by Jeremy Northam, and several of his songs were used for the film's soundtrack, including "Waltz of My Heart", "And Her Mother Came Too", "I Can Give You the Starlight", "What a Duke Should Be", "Why Isn't It You?" and "The Land of Might-Have-Been".

text: Songs[edit]

text: Among Novello's well-known songs are "Keep the Home Fires Burning",[42] "Fold Your Wings", "Shine Through My Dreams", "Rose of England", "I Can Give You the Starlight", "And Her Mother Came Too", "My Dearest Dear", "The Land of Might-Have-Been", "When I Curtsied to the King", "We'll Gather Lilacs",[6] "Someday My Heart Will Awake", "Yesterday", "Waltz of My Heart", "Why Isn't It You", "My Life Belongs to You", "Fly Home Little Heart", "Take Your Girl" and "Primrose".

text: In Grove's Dictionary of Music and Musicians, Webb writes that although Novello's oeuvre is generally thought of as "romantic" and "Ruritanian", his music "was far more varied than his current reputation suggests." Webb contends that such romantic hits as "Someday My Heart Will Awake" were balanced by "rousing operetta choruses ... and jazz age numbers" while "'Rose of England' is a stately patriotic piece that stands comparison with Elgar or Walton".[3]

text: Filmography[edit]

text: Actor[edit]

text:
Year
Title
Role
Country

1920
The Call of the Blood

France

1920
Miarka: The Daughter of the Bear

France

1921
Carnival
Count Andrea Scipione
United Kingdom

1922
The Bohemian Girl
Thaddeus
United Kingdom

1923
The Man Without Desire
Count Vittorio Dandolo
Germany/United Kingdom

1923
The White Rose
Joseph Beaugarde
United States

1923
Bonnie Prince Charlie
Prince Charles Stuart
United Kingdom

1925
The Rat
Pierre Boucheron, 'the Rat'
United Kingdom

1926
The Triumph of the Rat
Pierre Boucheron, 'the Rat'
United Kingdom

1927
The Lodger
The Lodger
United Kingdom

1927
Downhill
Roddy Berwick
United Kingdom

1927
The Vortex
Nicky Lancaster
United Kingdom

1928
The Constant Nymph
Lewis Dodd
United Kingdom

1928
The Gallant Hussar
Lieutenant Stephen Alrik
Germany/United Kingdom

1928
A South Sea Bubble
Vernon Winslow
United Kingdom

1929
The Return of the Rat
Pierre Boucheron, 'the Rat'
United Kingdom

1930
Symphony in Two Flats
David Kennard
United Kingdom

1931
Once a Lady
Bennett Cloud
United States

1932
The Lodger
Michel Angeloff
United Kingdom

1933
I Lived with You
Prince Felix Lenieff
United Kingdom

1933
Sleeping Car
Gaston
United Kingdom

1934
Autumn Crocus
Andreas Steiner
United Kingdom

text: Writer[edit]

text:
Year
Title
Country

1925
The Rat
United Kingdom

1926
The Triumph of the Rat
United Kingdom

1927
Downhill
United Kingdom

1929
The Return of the Rat
United Kingdom

1930
Symphony in Two Flats
United Kingdom

1932
Tarzan the Ape Man
United States

1932
But the Flesh Is Weak
United States

1932
The Lodger
United Kingdom

1933
I Lived with You
United Kingdom

1937
Glamorous Night
United Kingdom

1937
The Rat
United Kingdom

1941
Free and Easy
United States

1950
The Dancing Years
United Kingdom

1955
King's Rhapsody
United Kingdom

text: Notes[edit]

text:
Jump up ^ "Statue honours composer Novello", BBC News, 27 June 2009, accessed 26 September 2014
^ Jump up to: a b c d e f g h i j k l m n o p q r Snelson, John. "Novello, Ivor (1893–1951)", Oxford Dictionary of National Biography, Oxford University Press, 2004; online edition, January 2011, accessed 17 March 2011 (subscription required)
^ Jump up to: a b c d e f g Webb, Paul. "Novello, Ivor", Grove Music Online, Oxford Music Online, accessed 17 March 2011 (subscription required)
Jump up ^ MacQueen-Pope, p. 29
^ Jump up to: a b Trewin, J. C. "Popular Idol", The Times Literary Supplement, 18 May 1951, p. 304
^ Jump up to: a b c d e f Callow, Simon. "Ivor Novello, master of the musical", The Guardian, 3 August 2012
^ Jump up to: a b c d Obituary, The Times, 7 March 1951, p. 6
Jump up ^ Ibell, P. (2010) Theatreland: A Journey Through the Heart of London's Theatre, p. 89, London: Bloomsbury Continuum, ISBN 978-1847250032
Jump up ^ MacQueen-Pope, p. 120
Jump up ^ Grove Music Online states that the song dates from 1915, but the Oxford Dictionary of National Biography gives the date as 1914, a fact confirmed by the British Library catalogue
Jump up ^ MacQueen-Pope, pp. 57–62
Jump up ^ "Theodore & Co", The Play Pictorial, September 1916, p. 50
Jump up ^ Findon, B.W. "'Arlette' – An Operette in Three Acts", The Play Pictorial, November 1917, p. 82
Jump up ^ Hoare (1995), p.55
Jump up ^ Findon, B. W. "Who's Hooper?", The Play Pictorial, July 1919, p. 35
Jump up ^ "The Golden Moth", The Times, 6 October 1921, p. 8
^ Jump up to: a b "Ivor Novello", Encyclopedia of Popular Music, Oxford Music Online, accessed 16 March 2011 (subscription required)
Jump up ^ "The Theatres", The Times, 20 October 1921, p. 8
Jump up ^ "Plays of the Year", The Play Pictorial, October 1922, p. 111
Jump up ^ Roberts, p. 195
Jump up ^ Duguid, Mark. "The Man Without Desire (1923)",BFI Screen Online, accessed 14 June 2017
Jump up ^ It was credited to the pseudonymous David L'Estrange, but was the work of Novello and his friend, the actress Constance Collier: see ODNB
Jump up ^ "Duke of York's Theatre", The Times, 24 December 1926, p. 8
Jump up ^ Hoare (1995), p.123
Jump up ^ Hoare (1995), pp.187–88
Jump up ^ "The Theatres. Sirocco to be Withdrawn", The Times, 12 December 1927, p. 12
Jump up ^ Davies, John; Jenkins, Nigel; Menna, Baines; et al., eds. (2008). The Welsh Academy Encyclopaedia of Wales. Cardiff: University of Wales Press. p. 626. ISBN 978-0-7083-1953-6.
Jump up ^ According to the ODNB, "he reputedly originated the line that gave rise to the now mythical if inaccurate 'Me Tarzan. You Jane' (originally – with appropriate pointing – 'Tarzan. Jane.')"
Jump up ^ Letter from Novello to Coward, undated, in Day, p. 156
Jump up ^ Theatres", The Times, 2 May 1935, p. 12; and 18 July 1936, p. 12
Jump up ^ "Drury Lane", The Times, 12 September 1936, p. 10; and Gaye, p. 1529
Jump up ^ Gaye, p. 1530
Jump up ^ MacQueen-Pope, p. 234. The offending fan, Dora Grace Constable, escaped with a £50 fine: see ODNB
Jump up ^ Hoare (1995), p.349; Coward's modified sympathy was later echoed in Ewan MacColl's song "Ivor": see MacColl, Ewan. Bad Lads and Hard Cases, Riverside LP 1957
Jump up ^ Gaye, p. 1533
Jump up ^ Wilson, Scott. Resting Places: The Burial Sites of More Than 14,000 Famous Persons, 3d ed.: 2. McFarland & Company (2016) ISBN 0786479922
Jump up ^ "Composer Left £160,000 Estate.". The Mercury (Hobart, Tas. : 1860 – 1954). Hobart, Tas.: National Library of Australia. 9 June 1951. p. 8. Retrieved 10 July 2012.
Jump up ^ Pegler, Martin. Soldiers' Songs and Slang of the Great War, Osprey Publishing, 2014, p. 248 ISBN 9781427804150
Jump up ^ "Ivor Novello plaque, Aldwych", Geograph.org, accessed 26 September 2014
Jump up ^ "Statue honours composer Novello", BBC News, 27 June 2009
Jump up ^ "About us", Redroofs Associates, accessed 16 March 2011
Jump up ^ 1917 mp3 recording of "Keep the home fires burning" sung by John McCormack, firstworldwar.com, accessed 20 November 2009