document_title: Muscle contraction

question_text: what form of exercise does the muscle contract and does not lengthen nor shorten

text: Muscle contraction

text: Types[edit]

text: Muscle contractions can be described based on two variables: force and length. Force itself can be differentiated as either tension or load. Muscle tension is the force exerted by the muscle on an object whereas a load is the force exerted by an object on the muscle.[1] When muscle tension changes without any corresponding changes in muscle length, the muscle contraction is described as isometric.[1][3][4][5] If the muscle length changes while muscle tension remains the same, then the muscle contraction is isotonic.[1][3][4][5] In an isotonic contraction, the muscle length can either shorten to produce a concentric contraction or lengthen to produce an eccentric contraction.[1][6] Furthermore, if the muscle length shortens, the contraction is concentric.[1][6] But if the muscle length lengthens, then the contraction is eccentric. In natural movements that underlie locomotor activity, muscle contractions are multifaceted as they are able to produce changes in length and tension in a time-varying manner.[7] Therefore, neither length nor tension is likely to remain constant when the muscle is active during locomotor activity.

text: Isometric contraction[edit]

text: An isometric contraction of a muscle generates tension without changing length.[1][3][4][5] An example can be found when the muscles of the hand and forearm grip an object; the joints of the hand do not move, but muscles generate sufficient force to prevent the object from being dropped.

text: Isotonic contraction[edit]

text: In isotonic contraction, the tension in the muscle remains constant despite a change in muscle length.[1][3][4][5] This occurs when a muscle's force of contraction matches the total load on the muscle.

text: Concentric contraction[edit]

text: In concentric contraction, muscle tension is sufficient to overcome the load, and the muscle shortens as it contracts.[8] This occurs when the force generated by the muscle exceeds the load opposing its contraction.

text: During a concentric contraction, a muscle is stimulated to contract according to the sliding filament theory. This occurs throughout the length of the muscle, generating a force at the origin and insertion, causing the muscle to shorten and changing the angle of the joint. In relation to the elbow, a concentric contraction of the biceps would cause the arm to bend at the elbow as the hand moved from the leg to the shoulder (a biceps curl). A concentric contraction of the triceps would change the angle of the joint in the opposite direction, straightening the arm and moving the hand towards the leg.

text: Eccentric contraction[edit]

text: In eccentric contraction, the tension generated is insufficient to overcome the external load on the muscle and the muscle fibers lengthen as they contract.[9] Rather than working to pull a joint in the direction of the muscle contraction, the muscle acts to decelerate the joint at the end of a movement or otherwise control the repositioning of a load. This can occur involuntarily (e.g., when attempting to move a weight too heavy for the muscle to lift) or voluntarily (e.g., when the muscle is 'smoothing out' a movement). Over the short-term, strength training involving both eccentric and concentric contractions appear to increase muscular strength more than training with concentric contractions alone.[10] However, exercise-induced muscle damage is also greater during lengthening contractions.[11]

text: During an eccentric contraction of the biceps muscle, the elbow starts the movement while bent and then straightens as the hand moves away from the shoulder. During an eccentric contraction of the triceps muscle, the elbow starts the movement straight and then bends as the hand moves towards the shoulder. Desmin, titin, and other z-line proteins are involved in eccentric contractions, but their mechanism is poorly understood in comparison to crossbridge cycling in concentric contractions.[9]

text: Though the muscle is doing a negative amount of mechanical work, (work is being done on the muscle), chemical energy (in fat, glucose or ATP) is nevertheless consumed, although less than would be consumed during a concentric contraction of the same force. For example, one expends more energy going up a flight of stairs than going down the same flight.

text: Muscles undergoing heavy eccentric loading suffer greater damage when overloaded (such as during muscle building or strength training exercise) as compared to concentric loading. When eccentric contractions are used in weight training, they are normally called negatives. During a concentric contraction, muscle fibers slide across each other, pulling the Z-lines together. During an eccentric contraction, the filaments slide past each other the opposite way, though the actual movement of the myosin heads during an eccentric contraction is not known. Exercise featuring a heavy eccentric load can actually support a greater weight (muscles are approximately 40% stronger during eccentric contractions than during concentric contractions) and also results in greater muscular damage and delayed onset muscle soreness one to two days after training. Exercise that incorporates both eccentric and concentric muscular contractions (i.e., involving a strong contraction and a controlled lowering of the weight) can produce greater gains in strength than concentric contractions alone.[10][12] While unaccustomed heavy eccentric contractions can easily lead to overtraining, moderate training may confer protection against injury.[10]

text: Eccentric contractions in movement[edit]

text: Eccentric contractions normally occur as a braking force in opposition to a concentric contraction to protect joints from damage. During virtually any routine movement, eccentric contractions assist in keeping motions smooth, but can also slow rapid movements such as a punch or throw. Part of training for rapid movements such as pitching during baseball involves reducing eccentric braking allowing a greater power to be developed throughout the movement.

text: Eccentric contractions are being researched for their ability to speed rehabilitation of weak or injured tendons. Achilles tendinitis [13][14] and patellar tendonitis [15] (also known as jumper's knee or patellar tendonosis) have been shown to benefit from high-load eccentric contractions.

text: Vertebrate animals[edit]

text: In vertebrate animals, there are three types of muscle tissues: skeletal, smooth, and cardiac. Skeletal muscle constitutes the majority of muscle mass in the body and is responsible for locomotor activity. Smooth muscle forms blood vessels, gastrointestinal tract, and other areas in the body that produce sustained contractions. Cardiac muscle make up the heart, which pumps blood. Skeletal and cardiac muscles are called striated muscle because of their striped appearance under a microscope, which is due to the highly organized alternating pattern of A bands and I bands.

text: Skeletal muscle[edit]

text: Excluding reflexes, all skeletal muscles contractions occur as a result of conscious effort originating in the brain. The brain sends electrochemical signals through the nervous system to the motor neuron that innervates several muscle fibers.[16] In the case of some reflexes, the signal to contract can originate in the spinal cord through a feedback loop with the grey matter. Other actions such as locomotion, breathing, and chewing have a reflex aspect to them: the contractions can be initiated both consciously or unconsciously.

text: Neuromuscular junction[edit]

text: A neuromuscular junction is a chemical synapse formed by the contact between a motor neuron and a muscle fiber.[17] It is the site in which a motor neuron transmits a signal to a muscle fiber to initiate muscle contraction. The sequence of events that results in the depolarization of the muscle fiber at the neuromuscular junction begins when an action potential is initiated in the cell body of a motor neuron, which is then propagated by saltatory conduction along its axon toward the neuromuscular junction. Once it reaches the terminal bouton, the action potential causes a Ca2+ ion influx into the terminal by way of the voltage-gated calcium channels. The Ca2+ influx causes synaptic vesicles containing the neurotransmitter acetylcholine to fuse with the plasma membrane, releasing acetylcholine into the synaptic cleft between the motor neuron terminal and the neuromuscular junction of the skeletal muscle fiber. Acetylcholine diffuses across the synapse and binds to and activates nicotinic acetylcholine receptors on the neuromuscular junction. Activation of the nicotinic receptor opens its intrinsic sodium/potassium channel, causing sodium to rush in and potassium to trickle out. As a result, the sarcolemma reverses polarity and its voltage quickly jumps from the resting membrane potential of -90mV to as high as +75mV as sodium enters. The membrane potential then becomes hyperpolarized when potassium exits and is then adjusted back to the resting membrane potential. This rapid fluctuation is called the end-plate potential [18] The voltage-gated ion channels of the sarcolemma next to the end plate open in response to the end plate potential. These voltage-gated channels are sodium and potassium specific and only allow one through. This wave of ion movements creates the action potential that spreads from the motor end plate in all directions.[18] If action potentials stop arriving, then acetylcholine ceases to be released from the terminal bouton. The remaining acetylcholine in the synaptic cleft is either degraded by active acetylcholine esterase or reabsorbed by the synaptic knob and none is left to replace the degraded acetylcholine.

text: Excitation-contraction coupling[edit]

text: Excitation–contraction coupling is the process by which a muscular action potential in the muscle fiber causes the myofibrils to contract.[19] In skeletal muscle, excitation–contraction coupling relies on a direct coupling between key proteins, the sarcoplasmic reticulum (SR) calcium release channel (identified as the ryanodine receptor, RyR) and voltage-gated L-type calcium channels (identified as dihydropyridine receptors, DHPRs). DHPRs are located on the sarcolemma (which includes the surface sarcolemma and the transverse tubules), while the RyRs reside across the SR membrane. The close apposition of a transverse tubule and two SR regions containing RyRs is described as a triad and is predominantly where excitation–contraction coupling takes place. Excitation–contraction coupling occurs when depolarization of skeletal muscle cell results in a muscle action potential, which spreads across the cell surface and into the muscle fiber's network of T-tubules, thereby depolarizing the inner portion of the muscle fiber. Depolarization of the inner portions activates dihydropyridine receptors in the terminal cisternae, which are in close proximity to ryanodine receptors in the adjacent sarcoplasmic reticulum. The activated dihydropyridine receptors physically interact with ryanodine receptors to activate them via foot processes (involving conformational changes that allosterically activates the ryanodine receptors). As the ryanodine receptors open, Ca2+ is released from the sarcoplasmic reticulum into the local junctional space, which then diffuses into the bulk cytoplasm to cause a calcium spark. Note that the sarcoplasmic reticulum has a large calcium buffering capacity partially due to a calcium-binding protein called calsequestrin. The near synchronous activation of thousands of calcium sparks by the action potential causes a cell-wide increase in calcium giving rise to the upstroke of the calcium transient. The Ca2+ released into the cytosol binds to Troponin C by the actin filaments, to allow crossbridge cycling, producing force and, in some situations, motion. The sarco/endoplasmic reticulum calcium-ATPase (SERCA) actively pumps Ca2+ back into the sarcoplasmic reticulum. As Ca2+ declines back to resting levels, the force declines and relaxation occurs.

text: Sliding filament theory[edit]

text: The sliding filament theory describes a process used by muscles to contract. It is a cycle of repetitive events that cause a thin filament to slide over a thick filament and generate tension in the muscle.[20] It was independently developed by Andrew Huxley and Rolf Niedergerke and by Hugh Huxley and Jean Hanson in 1954.[21][22] Physiologically, this contraction is not uniform across the sarcomere; the central position of the thick filaments becomes unstable and can shift during contraction. However the actions of elastic proteins such as titin are hypothesised to maintain uniform tension across the sarcomere and pull the thick filament into a central position.[23]

text: Crossbridge cycling[edit]

text: Crossbridge cycling is a sequence of molecular events that underlies the sliding filament theory. A crossbridge is a myosin projection, consisting of two myosin heads, that extends from the thick filaments.[1] Each myosin head has two binding sites: one for ATP and another for actin. The binding of ATP to a myosin head detaches myosin from actin, thereby allowing myosin to bind to another actin molecule. Once attached, the ATP is hydrolyzed by myosin, which uses the released energy to move into the "cocked position" whereby it binds weakly to a part of the actin binding site. The remainder of the actin binding site is blocked by tropomyosin.[24] With the ATP hydrolyzed, the cocked myosin head now contains ADP + Pi. Two Ca2+ ions bind to troponin C on the actin filaments. The troponin-Ca2+ complex causes tropomyosin to slide over and unblock the remainder of the actin binding site. Unblocking the rest of the actin binding sites allows the two myosin heads to close and myosin to bind strongly to actin.[24] The myosin head then releases the inorganic phosphate and initiates a power stroke, which generates a force of 2 pN. The power stroke moves the actin filament inwards, thereby shortening the sarcomere. Myosin then releases ADP but still remains tightly bound to actin. At the end of the power stroke, ADP is released from the myosin head, leaving myosin attached to actin in a rigor state until another ATP binds to myosin. A lack of ATP would result in the rigor state characteristic of rigor mortis. Once another ATP binds to myosin, the myosin head will again detach from actin and another crossbridges cycle occurs.

text: Crossbridge cycling is able to continue as long as there are sufficient amounts of ATP and Ca2+ in the cytoplasm.[24] Termination of crossbridge cycling can occur when Ca2+ is actively pumped back into the sarcoplasmic reticulum. When Ca2+ is no longer present on the thin filament, the tropomyosin changes conformation back to its previous state so as to block the binding sites again. The myosin ceases binding to the thin filament, and the muscle relaxes. The Ca2+ ions leave the troponin molecule in order to maintain the Ca2+ ion concentration in the sarcoplasm. The active pumping of Ca2+ ions into the sarcoplasmic reticulum creates a deficiency in the fluid around the myofibrils. This causes the removal of Ca2+ ions from the troponin. Thus, the tropomyosin-troponin complex again covers the binding sites on the actin filaments and contraction ceases.

text: Gradation of skeletal muscle contractions[edit]

text: The strength of skeletal muscle contractions can be broadly separated into twitch, summation, and tetanus. A twitch is a single contraction and relaxation cycle produced by an action potential within the muscle fiber itself.[25] The time between a stimulus to the motor nerve and the subsequent contraction of the innervated muscle is called the latent period, which usually takes about 10 ms and is caused by the time taken for nerve action potential to propagate, the time for chemical transmission at the neuromuscular junction, then the subsequent steps in excitation-contraction coupling.[26]

text: If another muscle action potential were to be produced before the complete relaxation of a muscle twitch, then the next twitch will simply sum onto the previous twitch, thereby producing a summation. Summation can be achieved in two ways:[27] frequency summation and multiple fiber summation. In frequency summation, the force exerted by the skeletal muscle is controlled by varying the frequency at which action potentials are sent to muscle fibers. Action potentials do not arrive at muscles synchronously, and, during a contraction, some fraction of the fibers in the muscle will be firing at any given time. In a typical circumstance, when a human is exerting a muscle as hard as he/she is consciously able, roughly one-third of the fibers in that muscle will be firing at once, though this ratio can be affected by various physiological and psychological factors (including Golgi tendon organs and Renshaw cells). This 'low' level of contraction is a protective mechanism to prevent avulsion of the tendon—the force generated by a 95% contraction of all fibers is sufficient to damage the body. In multiple fiber summation, if the central nervous system sends a weak signal to contract a muscle, the smaller motor units, being more excitable than the larger ones, are stimulated first. As the strength of the signal increases, more motor units are excited in addition to larger ones, with the largest motor units having as much as 50 times the contractile strength as the smaller ones. As more and larger motor units are activated, the force of muscle contraction becomes progressively stronger. A concept known as the size principle, allows for a gradation of muscle force during weak contraction to occur in small steps, which then become progressively larger when greater amounts of force are required.

text: Finally, if the frequency of muscle action potentials increases such that the muscle contraction reaches its peak force and plateaus at this level, then the contraction is a tetanus.

text: Length-tension relationship[edit]

text: Length-tension relationship relates the strength of an isometric contraction to the length of the muscle at which the contraction occurs. Muscles operate with greatest active tension when close to an ideal length (often their resting length). When stretched or shortened beyond this (whether due to the action of the muscle itself or by an outside force), the maximum active tension generated decreases.[28] This decrease is minimal for small deviations, but the tension drops off rapidly as the length deviates further from the ideal. Due to the presence of elastic proteins within a muscle cell (such as titin) and extracellular matrix, as the muscle is stretched beyond a given length, there is an entirely passive tension, which opposes lengthening. Combined together, there is a strong resistance to lengthening an active muscle far beyond the peak of active tension.

text: Force-velocity relationships[edit]

text: Force–velocity relationship relates the speed at which a muscle changes its length (usually regulated by external forces, such as load or other muscles) to the amount of force that it generates. Force declines in a hyperbolic fashion relative to the isometric force as the shortening velocity increases, eventually reaching zero at some maximum velocity. The reverse holds true for when the muscle is stretched – force increases above isometric maximum, until finally reaching an absolute maximum. This intrinsic property of active muscle tissue plays a role in the active damping of joints which are actuated by simultaneously-active opposing muscles. In such cases, the force-velocity profile enhances the force produced by the lengthening muscle at the expense of the shortening muscle. This favoring of whichever muscle returns the joint to equilibrium effectively increases the damping of the joint. Moreover, the strength of the damping increases with muscle force. The motor system can thus actively control joint damping via the simultaneous contraction (co-contraction) of opposing muscle groups.[29]

text: Smooth muscle[edit]

text: Smooth muscles can be divided into two subgroups: single-unit (unitary) and multi-unit. Single-unit smooth muscle cells can be found in the gut and blood vessels. Because these cells are linked together by gap junctions, they are able to contract as a syncytium. Single-unit smooth muscle cells contract myogenically, which can be modulated by the autonomic nervous system.

text: Unlike single-unit smooth muscle cells, multi-unit smooth muscle cells are found in the muscle of the eye and in the base of hair follicles. Multi-unit smooth muscle cells contract by being separately stimulated by nerves of the autonomic nervous system. As such, they allow for fine control and gradual responses, much like motor unit recruitment in skeletal muscle.

text: Mechanisms of smooth muscle contraction[edit]

text: The contractile activity of smooth muscle cells is influenced by multiple inputs such as spontaneous electrical activity, neural and hormonal inputs, local changes in chemical composition, and stretch.[1] This is in contrast to the contractile activity of skeletal muscle cells, which relies on a single neural input. Some types of smooth muscle cells are able to generate their own action potentials spontaneously, which usually occur following a pacemaker potential or a slow wave potential. These action potentials are generated by the influx of extracellular Ca2+, and not Na+. Like skeletal muscles, cytosolic Ca2+ ions are also required for crossbridge cycling in smooth muscle cells.

text: The two sources for cytosolic Ca2+ in smooth muscle cells are the extracellular Ca2+ entering through calcium channels and the Ca2+ ions that are released from the sarcoplasmic reticulum. The elevation of cytosolic Ca2+ results in more Ca2+ binding to calmodulin, which then binds and activates myosin light-chain kinase. The calcium-calmodulin-myosin light-chain kinase complex phosphorylates myosin on the 20 kilodalton (kDa) myosin light chains on amino acid residue-serine 19, initiating contraction and activating the myosin ATPase. Unlike skeletal muscle cells, smooth muscle cells lack troponin, even though they contain the thin filament protein tropomyosin and other notable proteins – caldesmon and calponin. Thus, smooth muscle contractions are initiated by the Ca2+-activated phosphorylation of myosin rather than Ca2+ binding to the troponin complex that regulates myosin binding sites on actin like in skeletal and cardiac muscles.

text: Termination of crossbridge cycling (and leaving the muscle in latch-state) occurs when myosin light chain phosphatase removes the phosphate groups from the myosin heads. Phosphorylation of the 20 kDa myosin light chains correlates well with the shortening velocity of smooth muscle. During this period, there is a rapid burst of energy utilization as measured by oxygen consumption. Within a few minutes of initiation, the calcium level markedly decreases, the 20 kDa myosin light chains' phosphorylation decreases, and energy utilization decreases; however, force in tonic smooth muscle is maintained. During contraction of muscle, rapidly cycling crossbridges form between activated actin and phosphorylated myosin, generating force. It is hypothesized that the maintenance of force results from dephosphorylated "latch-bridges" that slowly cycle and maintain force. A number of kinases such as rho kinase, ZIP kinase, and protein kinase C are believed to participate in the sustained phase of contraction, and Ca2+ flux may be significant.

text: Neuromodulation[edit]

text: Although smooth muscle contractions are myogenic, the rate and strength of their contractions can be modulated by the autonomic nervous system. Postganglionic nerve fibers of parasympathetic nervous system release the neurotransmitter acetylcholine, which binds to muscarinic acetylcholine receptors (mAChRs) on smooth muscle cells. These receptors are metabotropic, or G-protein coupled receptors that initiate a second messenger cascade. Conversely, postganglionic nerve fibers of the sympathetic nervous system release the neurotransmitters epinephrine and norepinephrine, which bind to adrenergic receptors that are also metabotropic. The exact effects on the smooth muscle depend on the specific characteristics of the receptor activated—both parasympathetic input and sympathetic input can be either excitatory (contractile) or inhibitory (relaxing).

text: Cardiac muscle[edit]

text: There are two types of cardiac muscle cells: autorhythmic and contractile. Autorhythmic cells do not contract, but instead set the pace of contraction for other cardiac muscle cells, which can be modulated by the autonomic nervous system. In contrast, contractile muscle cells (cardiomyocytes) constitute the majority of the heart muscle and are able to contract.

text: Excitation-contraction coupling[edit]

text: Unlike skeletal muscle, excitation–contraction coupling in cardiac muscle is thought to depend primarily on a mechanism called calcium-induced calcium release.[30] Though the proteins involved are similar, the L-type calcium channels and ryanodine receptors (RyRs) are not physically coupled. Instead, RyRs are activated by a calcium trigger, which is brought about by the flow of Ca2+through the L-type calcium channels. Furthermore, cardiac muscle tend to exhibit diad (or dyad) structures, rather than triads.

text: Excitation-contraction coupling in cardiac muscle cells occurs when an action potential is initiated by pacemaker cells in the sinoatrial node or Atrioventricular node and conducted to all cells in the heart via gap junctions. The action potential travels along the surface membrane into T-tubules (the latter are not seen in all cardiac cell types) and the depolarisation causes extracellular Ca2+ to enter the cell via L-type calcium channels and possibly sodium-calcium exchanger (NCX) during the early part of the plateau phase. This Ca2+ influx causes a small local increase in intracellular Ca2+. The increase in Ca2+ is detected by ryanodine receptors in the membrane of the sarcoplasmic reticulum which releases Ca2+ in a positive feedback physiological response. This positive feedback is known as calcium-induced calcium release [30] and gives rise to calcium sparks (Ca2+ sparks[31]). The spatial and temporal summation of ~30,000 Ca2+ sparks gives a cell-wide increase in cytoplasmic calcium concentration.[32] The increase in cytosolic calcium following the flow of calcium through the cell membrane and sarcoplasmic reticulum is moderated by calcium buffers which bind a large proportion of intracellular calcium. As a result, a large increase in total calcium leads to a relatively small rise in free Ca2+.[33]

text: The cytoplasmic calcium binds to Troponin C, moving the tropomyosin complex off the actin binding site allowing the myosin head to bind to the actin filament. From this point on, the contractile mechanism is essentially the same as for skeletal muscle (above). Briefly, using ATP hydrolysis, the myosin head pulls the actin filament toward the centre of the sarcomere.

text: Following systole, intracellular calcium is taken up by the sarco/endoplasmic reticulum ATPase (SERCA) pump back into the sarcoplasmic reticulum ready for the next cycle to begin. Calcium is also ejected from the cell mainly by the sodium-calcium exchanger (NCX) and, to a lesser extent, a plasma membrane calcium ATPase. Some calcium is also taken up by the mitochondria.[34] An enzyme, phospholamban, serves as a brake for SERCA. At low heart rates, phospholamban is active and slows down the activity of the ATPase so that Ca2+ does not have to leave the cell entirely. At high heart rates, phospholamban is phosphorylated and deactivated thus taking most Ca2+ from the cytoplasm back into the sarcoplasmic reticulum. Once again, calcium buffers moderate this fall in Ca2+concentration, permitting a relatively small decrease in free Ca2+concentration in response to a large change in total calcium. The falling Ca2+concentration allows the troponin complex to dissociate from the actin filament thereby ending contraction. The heart relaxes, allowing the ventricles to fill with blood and begin the cardiac cycle again.

text: Invertebrate animals[edit]

text: Circular and longitudinal muscles[edit]

text: In annelids such as earthworms and leeches, circular and longitudinal muscles cells form the body wall of these animals and are responsible for their movement.[35] In an earthworm that is moving through a soil, for example, contractions of circular and longitudinal muscles occur reciprocally while the coelomic fluid serves as a hydroskeleton by maintaining turgidity of the earthworm.[36] When the circular muscles in the anterior segments contract, the anterior portion of animal's body begins to constrict radially, which pushes the incompressible coelomic fluid forward and increasing the length of the animal. As a result, the front end of the animal moves forward. As the front end of the earthworm becomes anchored and the circular muscles in the anterior segments become relaxed, a wave of longitudinal muscle contractions passes backwards, which pulls the rest of animal's trailing body forward.[35][36] These alternating waves of circular and longitudinal contractions is called peristalsis, which underlies the creeping movement of earthworms.

text: Obliquely striated muscles[edit]

text: Invertebrates such as annelids, mollusks, and nematodes, possess obliquely striated muscles, which contain bands of thick and thin filaments that are arranged helically rather than transversely, like in vertebrate skeletal or cardiac muscles.[37] In bivalves, the obliquely striated muscles can maintain tension over long periods without using too much energy. Bivalves use these muscles to keep their shells closed.

text: Asynchronous muscles[edit]

text: Advanced insects such as wasps, flies, bees, and beetles possess asynchronous muscles that constitute the flight muscles in these animals.[37] These flight muscles are often called fibrillar muscles because they contain myofibrils that are thick and conspicuous.[38] A remarkable feature of these muscles is that they do not require stimulation for each muscle contraction. Hence, they are called asynchronous muscles because the number of contractions in these muscles do not correspond (or synchronize) with the number of action potentials. For example, a wing muscle of a tethered fly may receive action potentials at a frequency of 3 Hz but it is able to beat at a frequency of 120 Hz.[37] The high frequency beating is made possible because the muscles are connected to a resonant system, which is driven to a natural frequency of vibration.

text: History[edit]

text: In 1780, Luigi Galvani discovered that the muscles of dead frogs' legs twitched when struck by an electrical spark.[40] This was one of the first forays into the study of bioelectricity, a field that still studies the electrical patterns and signals in tissues such as nerves and muscles.

text: In 1952, the term excitation–contraction coupling was coined to describe the physiological process of converting an electrical stimulus to a mechanical response.[19] This process is fundamental to muscle physiology, whereby the electrical stimulus is usually an action potential and the mechanical response is contraction. Excitation–contraction coupling can be dysregulated in many diseases.Though excitation–contraction coupling has been known for over half a century, it is still an active area of biomedical research. The general scheme is that an action potential arrives to depolarize the cell membrane. By mechanisms specific to the muscle type, this depolarization results in an increase in cytosolic calcium that is called a calcium transient. This increase in calcium activates calcium-sensitive contractile proteins that then use ATP to cause cell shortening.

text: The mechanism for muscle contraction evaded scientists for years and requires continued research and updating.[41] The sliding filament theory was independently developed by Andrew F. Huxley and Rolf Niedergerke and by Hugh Huxley and Jean Hanson. Their findings were published as two consecutive papers published in the 22 May 1954 issue of Nature under the common theme "Structural Changes in Muscle During Contraction".[21][22]


document_title: The Cleveland Show

question_text: who plays the voice of donna on the cleveland show

root

text: The Cleveland Show

text: Production[edit]

text: Development[edit]

text: Seth MacFarlane initially conceived The Cleveland Show in 2007 while working on his other two animated series, Family Guy and American Dad![2][3]

tag: p

text: The Cleveland Show first appeared on the development slate at Fox in early 2008, under no official name for the pilot, after a report that Fox had purchased the series from creators.[4] On May 5, 2008, MacFarlane and 20th Century Fox Television inked a deal.[5] The pilot was named The Cleveland Show in May 2008, when it appeared on the primetime slate for the 2008–09 television season, although it wasn't officially on the network schedule.[6] Shortly after a report that King of the Hill just ended, leaving air time for The Cleveland Show, the show was picked up for a full season after an additional nine episodes of the show were ordered.[7] In May 2009, The Cleveland Show appeared on the primetime slate for the 2009–10 television season, for airing on Sunday nights at 8:30 pm[8] On June 15, 2009, it was announced that The Cleveland Show would premiere on September 27, 2009.[9]

text: MacFarlane and Henry pitched a 22-minute pilot to Fox which aired on September 27, 2009, but had been leaked on the internet in June 2009. Even before the pilot episode premiered, the show had already been renewed for a 22-episode second season. After the first season of the show aired, it was given the green light to start production. On June 10, 2010, less than three weeks into the first season's summer hiatus, it was announced that Fox was ordering a third season.[10] A fourth season was announced on May 9, 2011, just a few days before the second season concluded.

text: Executive producers[edit]

text: Seth MacFarlane, Mike Henry and Richard Appel served as executive producers on the series since the first season.[11]

text: Voice cast[edit]

text: Mike Henry voices two of the show's main characters: Cleveland Brown and Rallo Tubbs. The voice of Cleveland was developed originally for Family Guy by Henry after being influenced by one of his best friends who had a very distinct regional accent.[12] For the voice of Rallo, Henry has stated that he had originally created the voice over twenty years ago, when he had made a series of prank calls.

text: Sanaa Lathan voices Donna Tubbs, the wife of Cleveland, and Cleveland Brown Jr. Stepmom and Ex-wife of Roberta and Rallo's Dad, Robert Tubbs. In developing the character, Lathan said that the producers "wanted her to be educated, but to have some edge."[13] Prior to voicing Donna, Lathan had only one other voice credit in a relatively low-budget film entitled The Golden Blaze. In addition to the show, she also primarily worked as an actress in such films as Alien vs. Predator, Love & Basketball and The Family That Preys.

text: Reagan Gomez-Preston plays Roberta Tubbs, the stepdaughter of Cleveland. Gomez has stated that she uses her own voice to portray Roberta, and that she herself gets mistaken for a fifteen-year-old over the phone "all the time."[13] Before Gomez was cast as Roberta, Nia Long (who co-starred with Lathan in The Best Man franchise) provided the character's voice during the first thirteen episodes. According to Long, she was replaced because producers decided they wanted an actress with a younger-sounding voice, given that the character is a teenager.[14]

text: Kevin Michael Richardson, a recurring guest voice on Family Guy and American Dad, portrays Cleveland, Jr., as well as Cleveland's next door neighbor Lester Krinklesac. In portraying Cleveland, Jr., Richardson drew inspiration from a character named Patrick that he had played on the NBC drama series ER who was mentally impaired and wore a football helmet. For Lester, Richardson stated in an interview that, being African American, he had "run into a few rednecks in [his] time," and decided to simply perform a stereotypical redneck impression for the voice of Lester.[13]

text: Jason Sudeikis plays Holt Richter, one of Cleveland's drinking buddies with a short stature, and Terry Kimple, one of Cleveland's longtime friends who now works with him at Waterman Cable. Sudeikis originally began as a recurring cast member, but starting with the episode "Harder, Better, Faster, Browner", he was promoted to a series regular.

text: Seth MacFarlane played Tim the Bear up until season 3 episode 10, which MacFarlane admits is a "Steve Martin impression [...] a Wild and Crazy Guy impression". Jess Harnell voices Tim from season 3 episode 11 onwards.

text: Other voices include that of Arianna Huffington as Tim's wife Arianna the Bear, Nat Faxon as Tim and Arianna's son Raymond the Bear, Jamie Kennedy as Roberta's boyfriend Gabriel Friedman, a.k.a. "Federline Jones", Will Forte as Principal Wally, Frances Callier as Evelyn "Cookie" Brown, Craig Robinson as LeVar "Freight Train" Brown and David Lynch as Gus the bartender.

text:
Main cast members

Mike Henry
Sanaa Lathan
Reagan Gomez-Preston
Kevin Michael Richardson
Jason Sudeikis
Seth MacFarlane

Cleveland Brown, Rallo Tubbs
Donna Tubbs
Roberta Tubbs
Cleveland Brown, Jr. and Lester Krinklesac
Holt Richter
and Terry Kimple
Tim the Bear

tag: table

text: Characters[edit]

text: Cleveland's newly introduced family includes his new wife in her early forties, Donna Tubbs Brown (voiced by Sanaa Lathan);[15] Donna's teenage daughter Roberta (originally voiced by Nia Long, but later voiced by Reagan Gomez-Preston); and Donna's five-year-old son Rallo (also voiced by Mike Henry).[16][17] Cleveland, Jr. underwent a complete redesign for the show, becoming sensitive and soft-spoken.

text: Episodes[edit]

text:
Season
Episodes
Originally aired
Nielsen ratings

First aired
Last aired
Rank
Viewers
(millions)

1
21
September 27, 2009 (2009-09-27)
May 23, 2010 (2010-05-23)
No. 72[18]
6.38[18]

2
22
September 26, 2010 (2010-09-26)
May 15, 2011 (2011-05-15)
No. 90[19]
6.12[19]

3
22
September 25, 2011 (2011-09-25)
May 20, 2012 (2012-05-20)
No. 144[20]
4.03[20]

4
23
October 7, 2012 (2012-10-07)
May 19, 2013 (2013-05-19)
No. 129[21]
3.05[21]

text: Crossovers with other animated sitcoms[edit]

text: The Cleveland Show characters have appeared on other animated sitcoms and vice versa. The Cleveland Show crossovers have all involved two other animated programs. Both the other two animated programs were also created by Seth MacFarlane: Family Guy and American Dad!

text: There are also many brief cameos of characters from other Fox animated series, The Simpsons, and King of the Hill.

text: Broadcast[edit]

text: Syndication[edit]

text: In July 2010, the Turner Broadcasting System picked up syndication rights, for their networks TBS and Adult Swim.[22] The series first aired in syndication on Adult Swim on Cartoon Network in the United States on September 29, 2012. In Canada, MuchMusic ran previews of the show on September 2, 2013, followed by its official debut on the next day.

text: Cancellation[edit]

text: On April 17, 2013, Fox dismissed increasing rumors that The Cleveland Show had been cancelled, reporting rather that renewal of the series was undetermined as of that time.[23][24] However, on May 13, 2013, in the New York Daily News, Fox Chairman of Entertainment Kevin Reilly confirmed its cancellation.[1] Following the series cancellation, it was confirmed that Cleveland and the Brown/Tubbs family would be moving back to Quahog to rejoin the Family Guy cast.[25]

text: International broadcast[edit]

text:
Country
Network
Premiere date

Canada
Global
MuchMusic
September 27, 2009 – May 19, 2013
September 3, 2013–August 31, 2017

Australia
Network Ten
Eleven
FOX8
December 2, 2009 – January 12, 2011
January 12, 2011 – 2014
March 13, 2011 – present

Germany
Comedy Central
August 7, 2016 – present

Lithuania
TV6
– present (Klyvlando Šou)

Ireland
3e
2009

United Kingdom
E4
Fox
ITV2
February 1, 2010 – Autumn 2015[26]
January 6, 2011 – ?
2016–Present [26]

United States
Fox
Adult Swim
TBS
September 27, 2009 – May 19, 2013
September 29, 2012 – present
September 16, 2013 – present

Hungary
Comedy Central
Humor+

July 6, 2010 – October 30, 2016
October 30, 2016 – present

Middle East
FX
Unknown

New Zealand
C4
Four
Comedy Central
2010
February 10, 2011 – present
2011–present

Pakistan
FX
Unknown

Philippines
Jack TV
Fox Philippines
October 2010 - Present (Rerun)
March 2013 - Present (Rerun)

South Africa
Vuzu
November 29, 2010

Singapore
Fox
April 2, 2012 (Season 2)
(Mondays to Wednesdays 11:40 pm (UTC+8))

text: Reception[edit]

text: Critical reception[edit]

text: The Cleveland Show has received mixed reviews from critics and negative reviews from fans. Review aggregator Metacritic gave the show a score of 57 out of 100.[27] Tom Shales of The Washington Post spoke very negatively about both the show and MacFarlane himself, describing him as "no better than the dirty old man hanging around playgrounds with naughty pictures or risque jokes as lures".[28] Roberto Bianco of USA Today wrote a similarly negative review, suggesting that the easiest fix for its problem was "cancellation".[29] John McWhorter of The New Republic called it "a patronizing mess" and "basically Family Guy in blackface". He added: "What isn't black in it is so shamelessly ripped off from Family Guy that it's hard to believe it's the product of creators who are usually so studiously 'post-' obvious stunts of the sort."[30] Matt Rouse of TV Guide wrote, "The lamest, most unnecessary spin-off since Private Practice, Cleveland rests on the shoulders of the hopelessly bland title character".[31] However, Rob Owen of the Pittsburgh Post-Gazette was more positive about the program, writing that although The Cleveland Show was "just as rude-crude" as Family Guy, it also had "more warmth" due to Cleveland being a more likeable character than Peter Griffin. Owen also praised the character of Tim the Bear, stating that "Tim is by far the most amusing creation."[32]

text: Awards and nominations[edit]

text:
Year
Award
Category
Recipients and nominees
Outcome

2010
Teen Choice Awards
Choice TV: Animated Show
The Cleveland Show
Nominated

People's Choice Awards
Favorite New TV Comedy
The Cleveland Show
Nominated

2011
Annie Awards
Best Voice Acting in an Animated Television Production
Mike Henry as Cleveland Brown
Nominated

Primetime Emmy Awards
Outstanding Animated Program
"Murray Christmas"
Nominated

NAMIC Vision Awards
Animation
The Cleveland Show
Nominated

Teen Choice Awards
Choice TV: Animated Show
The Cleveland Show
Nominated

2012
Artios Award
Outstanding Achievement in Casting – Television Animation
Robert McGee and Ruth Lambert
Nominated

2013
American Society of Composers, Authors and Publishers Awards
Top Television Series
The Cleveland Show
Won

People's Choice Awards
Favorite Cartoon Show
The Cleveland Show
Nominated

text: Home media[edit]

text: DVD releases[edit]

text:
DVD Title
# of Disc(s)
Year
# of Episodes
DVD release

Region 1
Region 2
Region 4

Season One
4
2009 & 2010
21
September 28, 2010[33]
October 11, 2010[34]
June 29, 2011[35]

Season Two
4
2010 & 2011
22
September 27, 2011[36]
January 30, 2012[37]
November 2, 2011[38]

Season Three
3
2011 & 2012
22
March 1, 2013[39]
(manufactured on demand (MOD) on DVD-R)

Season Four
3
2012 & 2013
23
December 17, 2013[40]
(manufactured on demand (MOD) on DVD-R)

text:
Animation portal
Comedy portal
Television portal

tag: ul


document_title: Gold reserve

question_text: where is the most gold in the world stored

text: Gold reserve

text: Wartime relevance[edit]

text: During most of history, a nation's gold reserves were considered its key financial asset and a major prize of war.

text: A typical view was expressed in a secret memorandum by the British Chief of the Imperial General Staff from October 1939, at the beginning of World War II. The British Military and the British Secret Service laid out "measures to be taken in the event of an invasion of Holland and Belgium by Germany" and presented them to the War Cabinet:

text: It will be for the Treasury in collaboration with the Bank of England, and the Foreign Office, to examine the possible means of getting the bullion and negotiable securities into the same place of safety. The transport of many hundreds of tons of bullion presents a difficult problem and the loading would take a long time. The ideal would of course be to have the gold transferred to this country or to the United States of America. [...] The gold reserves of Belgium and Holland amount to about £70 million and £110 million respectively. [Foot]Note: H. M. Treasury has particularly requested that this information, which is highly confidential should in no circumstances be divulged. The total weight of this bullion amounts to about 1800 tons and its evacuation would be a matter of the utmost importance would present a considerable problem if it had to be undertaken in a hurry when transport facilities were disorganized. At present this gold is believed to be stored at Brussels and The Hague respectively, neither of which is very well placed for its rapid evacuation in an emergency.[3]

text: The Belgian government rushed to ship the gold to a safe place: Dakar, the capital of Senegal, then part of the French colonial empire. After the Germans occupied Belgium and France in 1940, they demanded the Belgian gold reserve back. In 1941, Vichy French officials arranged the transport of 4,944 boxes with 198 tons of gold to officials of the German Reichsbank.[4]

text: IMF holdings[edit]

text: Since early 2011, the gold holdings of the IMF have been constant at 90.5 million troy ounces (2,814.1 metric tons).[5]

text: Officially reported holdings[edit]

text: The IMF regularly maintains statistics of national assets as reported by various countries.[6] This data is used by the World Gold Council to periodically rank and report the gold holdings of countries and official organizations.

text: On 17 July 2015, China announced that it increased its gold reserves by about 57 percent from 1,054 to 1,658 metric tons, while disclosing its official gold reserves for the first time in six years.[7][8]

text: The gold listed for each of the countries in the table may not be physically stored in the country listed, as central banks generally have not allowed independent audits of their reserves. Gold leasing by central banks could place into doubt the reported gold holdings in the table below.[9]

text:
Top 20 according to World Gold Council's latest rankings (as at September 2017)[10][11][12][13]

Rank
Country/Organization
Gold holdings
(in tonnes)
Gold's share of
forex reserves

1
 United States
8,133.5
74.6%

2
 Germany
3,374.1
69.1%

3
International Monetary Fund
2,814.0
N/A

4
 Italy
2,451.8
67.2%

5
 France
2,435.9
65.0%

6
 China
1,842.6
2.4%

7
 Russia
1,729.4
16.8%

8
  Switzerland
1,040.0
5.5%

9
 Japan
765.2
2.5%

10
 Netherlands
612.5
66.0%

11
 India
557.8
5.8%

12
 European Central Bank
504.8
24.0%

13
 Turkey[14]
482.9
18.3%

14
 Taiwan
423.6
3.7%

15
 Portugal
382.5
58.6%

16
 Saudi Arabia
322.9
2.6%

17
 United Kingdom
310.3
7.2%

18
 Lebanon
286.8
21.6%

19
 Spain
281.6
17.5%

20
 Kazakhstan
280.9
34.8%


document_title: Biliary tract

question_text: where does bile go after it leaves the gallbladder

text: Biliary tract

text: Structure[edit]

text: The biliary tract refers to the path by which bile is secreted by the liver then transported to the duodenum, the first part of the small intestine. A structure common to most members of the mammal family, the biliary tract is often referred to as a tree because it begins with many small branches which end in the common bile duct, sometimes referred to as the trunk of the biliary tree. The duct, the branches of the hepatic artery, and the portal vein form the central axis of the portal triad. Bile flows in the direction opposite to that of the blood present in the other two channels.

text: The system is usually referred to as the biliary tract or system, [1]and can include the use of the term "hepatobiliary" when used to refer just to the liver and bile ducts.[2] The name biliary tract is used to refer to all of the ducts, structures and organs involved in the production, storage and secretion of bile.[3]

text: The tract is as follows:

text:
Bile canaliculi >> Canals of Hering >> intrahepatic bile ductule (in portal tracts / triads) >> interlobular bile ducts >> left and right hepatic ducts >>
These merge to form the common hepatic duct
This exists the liver and joints with the cystic duct from gall bladder
Together these form the common bile duct which joins with the pancreatic duct
These pass through the ampulla of Vater and enter the duodenum

text: Function[edit]

text: Bile is secreted by the liver into small ducts that join to form the common hepatic duct. Between meals, secreted bile is stored in the gall bladder, where 80%-90% of the water and electrolytes can be absorbed, leaving the bile acids and cholesterol. During a meal, the smooth muscles in the gallbladder wall contract, leading to the bile being secreted into the duodenum to rid the body of waste stored in the bile as well as aid in the absorption of dietary fats and oils by solubilizing them using bile acids.

text: Clinical significance[edit]

text: Pressure inside in the biliary tree can give rise to gallstones and lead to cirrhosis of the liver.

text: The biliary tract can also serve as a reservoir for intestinal tract infections. Since the biliary tract is an internal organ, it has no somatic nerve supply, and biliary colic due to infection and inflammation of the biliary tract is not a somatic pain. Rather, pain may be caused by luminal distension, which causes stretching of the wall. This is the same mechanism that causes pain in bowel obstructions.[citation needed]

text: An obstruction of the biliary tract can result in jaundice, a yellowing of the skin and whites of the eyes. [4]