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Muscle - AccessScience from McGraw-Hill Education http://www.accessscience.com/content/muscle/439700

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Article by: Bock, Walter J. Department of Biological Sciences, Columbia University, New York, New York. Rainford, Patricia Natural History Museum, California Academy of Sciences, San Francisco, California. Last updated: 2014 DOI: https://doi.org/10.1036/1097-8542.439700 (https://doi.org/10.1036/1097-8542.439700)

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Anatomy Biophysics Calcium sensor Microstructure Length–tension relationship Mechanistic model Energy transformation Fueling reaction Links to Primary Literature Morphology Physiology Additional Readings

The in the body in which cellular contractility has become most apparent. Almost all forms of protoplasm exhibit some degree of contractility, but in muscle fibers specialization has led to the preeminence of this property.

In vertebrates three major types of muscle are recognized: smooth, cardiac, and skeletal.

Smooth muscle

Smooth muscle, also designated visceral and sometimes involuntary, is the simplest type. These muscles consist of elongated fusiform cells which contain a central oval nucleus. The length of such fibers varies greatly, from a few micrometers up to 0.02 in. (0.5 mm). These fibers contract relatively slowly and have the ability to maintain contraction for a long time. Smooth muscle forms the major contractile elements of the viscera, especially those of the respiratory and digestive tracts, and the blood vessels. Smooth muscle fibers in the regulate heat loss from the body. Those in the walls of various ducts and tubes in the body act to move the contents to their destinations, as in the biliary system, , and reproductive tubes.

Smooth muscle is usually arranged in sheets or layers, commonly oriented in different directions. The major physiological properties of these muscles are their intrinsic ability to contract spontaneously and their dual regulation by the autonomic nerves of the sympathetic and parasympathetic systems.

Cardiac muscle

Cardiac muscle has many properties in common with smooth muscle; for example, it is innervated by the autonomic system and retains the ability to contract spontaneously. Presumably, cardiac muscle evolved as a specialized type from the general smooth muscle of the circulatory vessels. Its rhythmic contraction begins early in embryonic development and continues until death. Variations in the rate of contraction are induced by autonomic regulation and by many other local and systemic factors. See also: (/content/autonomic-nervous-system/065000)

The cardiac fiber, like smooth muscle, has a central nucleus, but the cell is elongated and not symmetrical. It is a , a

1 of 12 6/13/17, 6:55 AM Muscle - AccessScience from McGraw-Hill Education http://www.accessscience.com/content/muscle/439700 multinuclear cell or a multicellular structure without cell walls. Histologically, cardiac muscle has cross-striations very similar to those of skeletal muscle, and dense transverse bands, the intercalated disks, which occur at short intervals.

The heart contains its own specialized system for initiation and spread of contraction in a wavelike form over the myocardium. This conducting system, which is composed of the sinoauricular and atrioventricular nodes and intervening bundles of special tissue, transmits the primary impulses. It is modified cardiac muscle, sometimes called the neuromuscular system to indicate its dual characteristics. See also: Heart (vertebrate) (/content/heart-vertebrate/309900)

Skeletal muscle

Skeletal muscle is also called striated, somatic, and voluntary muscle, depending on whether the description is based on the appearance, the location, or the innervation. The individual cells or fibers are distinct from one another and vary greatly in length from over 6 in. (15 cm) to less than 0.04 in. (1 mm). These fibers do not ordinarily branch, and they are surrounded by a complex membrane, the . Within each fiber are many nuclei; thus it is actually a syncytium formed by the fusion of many precursor cells.

The transverse striations of skeletal muscle form a characteristic pattern of light and dark bands within which are narrower bands. These bands are dependent upon the arrangement of the two sets of sliding filaments and the connections between them.

A number of different types of vertebrate skeletal fibers are known, including twitch and tonus, red and white, fast twitch and slow twitch, large- and small-diametered, and so forth. Details of the correlations between these and other properties of fiber types are far from satisfactorily known.

Morphology

When organized into muscles, skeletal muscle fibers are arranged in an orderly fashion with the axis of the fibers orienting roughly between the two points of muscle attachment. Surrounding the individual muscle fibers is a layer, the . Groups of fibers form bundles, or fasciculi, which are ensheathed with collagenous fibered connective tissue, the . This perimysium is continuous throughout the muscles and with the surrounding the entire muscle. These sheaths of connective tissue grade rather abruptly into the dense collagenous structure of at the ends of the muscle.

The size of a muscle—the number and length of fibers—is directly related to the function of that muscle. For a muscle of a fixed volume, the number of fibers is inversely proportional to the length of the fibers. Hence, as the number of fibers increases with the force development of the muscle, their length decreases with a reduction in the ability of the muscle to shorten. Conversely, as the fibers increase in length, allowing the muscle to shorten over a greater distance, its force decreases with the reduction in the number of fibers. Pinnate muscles have the fibers arranged obliquely to the central of the muscle, permitting a large number of shorter fibers to be packed into a conveniently shaped muscle. These muscles can develop great force but can shorten through a very restricted distance.

Skeletal muscles tend to be distributed about a movable structure (bone) so as to produce antagonistic actions, allowing the force of each muscle to relengthen the opposing muscle. In most parts of the body, movement of the bones is achieved through the synergistic contraction of groups of muscles rather than by the action of individual muscles.

The innervation of skeletal muscles by motor fibers of the peripheral nervous system presents a quite constant pattern. This pattern appears early in embryonic life when the motor nerves grow into the of each body segment. During the

2 of 12 6/13/17, 6:55 AM Muscle - AccessScience from McGraw-Hill Education http://www.accessscience.com/content/muscle/439700 ontogeny of limbs and specialized features of the trunk, neck, and head, a great deal of rearrangement occurs, but the early relationships are maintained so long as the muscle persists as a postembryonic structure. See also: (/content/muscular-system/440200)

Walter Bock

Muscle is a for generating mechanical force and requires the expenditure of free energy. A solution of (ATP) has substantially more free energy than its breakdown products adenosine diphosphate (ADP)

and inorganic phosphate (P i). The loss in free energy when ATP and water are converted into ADP and P i provides the required expenditure of energy for muscle. Thus ATP and water may be considered the fuel for operating the muscle machine. See also: Adenosine triphosphate (ATP) (/content/adenosine-triphosphate-atp/010700)

This energy expenditure may or may not permit the muscle to do useful work. If the force generated is applied to an immovable object, such as a weight too heavy to lift, the result is merely the generation of static tension in the muscle. The muscle is then said to be contracting isometrically—it is prevented by the heavy weight from changing length. If the force generated exceeds the weight, then the muscle, by shortening, will move the weight. Such a muscle is contracting isotonically. An animal normally employs both types of contraction; isometric contraction occurs in applying pressure or in holding the skeleton against gravitational forces, while isotonic contractions result in moving the skeleton.

All three types of muscle operate with the same machinery. The following discussion focuses on research on the contractile apparatus of vertebrate skeletal (striated) muscle.

Microstructure

A striated muscle is a cylindrical bundle of fibers; each fiber is, in turn, a cylindrical bundle of fibrils (). The myofibrils are segmented into , each a diminutive cylinder about 1 μm in diameter and 2.5 μm long. The sarcomeres of adjacent myofibrils are in register, thus giving the entire fiber a banded (or striated) appearance.

At either end the sarcomeres are bounded by end plates called Z membranes. The central sectors of sarcomeres are highly birefringent and are known as A (for anisotropic) bands, while the sections to either side of the Z members are practically nonbirefringent and are known as I (for isotropic) bands. Both the A and I bands result from the existence of two independent arrays of filaments which interpenetrate extensively in the A band (Fig. 1): these filament arrays are hexagonal in cross section (Fig. 2). Thin filaments are attached to each Z membrane and extend inward into the but are not continuous across it. Thick filaments exist in the central sector. When the fibril is at rest length, the thick and thin filaments interpenetrate, but the degree to which they do so varies with the length of the fibril. The relatively clear central zone separating the two edges of the thin filament arrays is called the H zone (Fig. 1). The Z membrane, which is common to two sarcomeres, is composed of a special weave. From an end-on view it is a cubic lattice, but in longitudinal section it shows thin filaments in a hexagonal array.

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Fig. 1 Schematic representation of two adjacent sarcomeres showing banding patterns as revealed by electron microscopy.

Fig. 2 Cross section of a muscle fibril.

Mechanistic model

It is possible to discuss the operation of muscle in mechanistic terms. In this sense a has three recognizable machines: the , the calcium sensor, and the contractile apparatus.

Sarcoplasmic reticulum

The sarcolemma () of a single muscle fiber is perforated in a regular manner by tubular invaginations (sarcotubules). In contact with these tubules are elongated flat sacs or cisternae which surround subbundles of fibrils like a blanket. Collectively these cisternae are known as the sarcoplasmic reticulum (Fig. 3). Both the sarcolemma and the walls of the cisternae are bilayered. There is no direct opening between the tubules and the cisternae; however, at the points of contact there are four distinct layers (Fig. 3b). Communication between tubules and cisternae is therefore not by passage of a transmitter substance but perhaps by a field effect. Like bilayered membranes of other cells, the membranous sarcoplasmic reticulum contains essential phospholipid and structural protein, as well as certain enzyme proteins. See also: Cell membranes (/content/cell-membranes/116500)

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Fig. 3 Schematic representations of the sarcoplasmic and sarcotubular systems. (a) Cutaway of a muscle fiber. (b) Cross section of a fiber. (c) Fiber viewed from above (sarcolemma removed) showing triad formation of tubule and cisternae.

In response to nerve signals the sarcoplasmic reticulum can explosively release calcium ions into the contractile apparatus. Contractile impulses are initiated at the motor end plates, which are the points of contact of the nerve endings with the muscle cell. The nerve endings release the chemical , and the muscle cell then initiates its own stimulus which is conducted along the sarcolemma to the tubules. The tubules extend inward to surround each at the Z membrane. From here the electrical signal is somehow transferred to the adjacent anastomosing sheath of cisternae surrounding each myofibril. Sodium and potassium ions are intimately involved in the transmission of the impulses or stimuli. As the stimulus wave travels along the sarcolemma, sodium ions move into the membrane and potassium ions move outward. This shift of cations is not matched by a corresponding shift of anions, and as a result of the change of electrical charge on either side of the membrane an electrical potential change is created which propagates the stimulus wave. As a result of the nerve impulse a transition occurs in the cisternae membranes, causing them to become more permeable and thereby creating a very leaky pump. Because of the ion gradient that exists, calcium ions diffuse out of the cisternae very rapidly. This explains the rapid contractile response to a nerve impulse, since it is the calcium ion (Ca2+ ) concentration which controls the contractile mechanism at the molecular level. The sarcoplasmic reticulum stores large amounts of Ca 2+ in the lumen of the cisternae. See also: Acetylcholine (/content/acetylcholine/003900); Biopotentials and ionic currents (/content/biopotentials- and-ionic-currents/083900)

After contraction, the electrical effect stops, the impermeability of the cisternae walls is restored, and calcium ion is pumped back into the cisternae, which brings about relaxation. Since calcium must move counter to the electrical gradient, this phase therefore requires work, is associated with ATP hydrolysis, and is another example of active transport.

Calcium sensor

This device is attached to the contractile apparatus and “reads” the ambient Ca2+ concentration. When adequate Ca2+ is present, it removes blocks and permits the apparatus to work. In the absence of Ca 2+ it restores these blocks and prevents the apparatus from contracting. This sensor device is described in more detail below.

Contractile apparatus

This machine is constructed from two proteins and runs on energy provided by magnesium ions (Mg2+ ) and ATP. Muscle fibers shorten or lengthen because their sarcomeres shorten or lengthen, that is, because the filaments within the sarcomeres translate (slide) relative to one another. The self-propelled, active shortening of fibers is always accompanied by the

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hydrolysis reaction, ATP + H 2O → ADP + Pi . Fibers lengthen or get stretched only when external forces are applied to them. An emerging generalization seems to be that all biological movement (such as all muscular, ameboid, and ciliary movement) is associated with the translation of filaments and with the hydrolysis of a triphosphate. However, the array arrangement, the proteins constituting the filaments, and the particular phosphate may differ from system to system.

The thin and thick filaments are principally composed of the proteins and , respectively (Fig. 4). Both filaments are polymeric and polar, and each is a serial arrangement of “building blocks” or monomers. One “end” of a monomer is different from the other, and in the serial arrangement of a filament the monomers are assembled “head to tail,” so that the filament itself has a direction. The actin filaments can be thought to originate at the Z disks of the sarcomere and to point toward a central midplate. Each thick filament can be thought of as consisting of two coaxial myosin filaments; both originate at the midplane, and each points to one Z disk. The midplate is thus a plane of symmetry for the sarcomere. The directions assigned to the filaments can be taken as the directions of relative when a sarcomere shortens.

Fig. 4 A sarcomere changing length (Z-Z distance). The thick and thin filaments, though remaining at constant length, translate relative to one another. The chevrons indicate the polarity and location of the molecules constituting the filaments. The number of myosin molecules next to actin differs at different extensions (A, B, C, D, E). Not shown in this schema is the fact that sarcomeres contract at constant volume, so that shortening is accompanied by separation of the filaments in the transverse directions.

In both actin and myosin filaments the serial arrangement of monomers is helical. In cross section these actin and myosin helices form a well-ordered lattice. The net result of this geometry is that parallel to the fiber axis some of a particular actin filament are closest to some of an adjacent myosin filament (the remainder of the actins are closest to other myosin filaments, and the remainder of the myosins are closest to other actin filaments). The ratio of actins to myosins need not be unity (it is in fact 5) because the pitches of the two types of helices need not be the same. See also: Muscle proteins (/content/muscle-proteins/439900)

Actin monomer

This monomer is a dumbbell-shaped, single-chain globular protein of about 42,000 daltons and a maximum dimension of about 5 nanometers. Actin in monomeric form is known as G-actin, while in the two-stranded helical polymer form it is known as F-actin. Under physiological conditions F-actin is insoluble. In F-actin each monomer is held to the monomer before and after it on the same strand, as well as to two monomers of the other strand. These four interactin bonds are not covalent, but are quite strong. Nevertheless, the F-actin filament is rather flexible, implying that the monomers themselves may be deformable under physiological conditions. Along the filament axis the F-actin double helix repeats every 13 monomers, or every 36 nm.

6 of 12 6/13/17, 6:55 AM Muscle - AccessScience from McGraw-Hill Education http://www.accessscience.com/content/muscle/439700 Myosin monomer

This monomer is a very long (about 150 nm) and very heavy (about 480,000 daltons) multichain molecule resembling a Y with a knob or head at the end of each arm (Fig. 5). The main structure of the Y consists of two heavy chains whose C-terminal (carboxyl end) regions are intertwined to form the stem, and whose N-terminal (amino end) regions unravel to form the arms and heads. Attached to each head is a set of two light chains, one of which (the regulatory light chain) contains a high-affinity Ca2+ -binding site and a reactive that can be phosphorylated. The amino acid composition of the light chains is often different among different muscle cells (for example, fast skeletal muscle, smooth muscle, and embryonic muscle). This circumstance gives rise to many myosin isozymes.

Fig. 5 Diagram of myosin, which is about 15 nm long. The various segments are obtainable after suitable proteolysis; light chains separate out in denaturing solvents. It is currently speculated that S-1 itself contains three domains.

By selective proteolysis it is possible to cut away and isolate just the heads of myosin. Such a head is known as a myosin subfragment 1 or S-1, while the remaining structure is known as a myosin rod. Proteolysis can again be used to cut this rod and generate two more segments; an N-terminal myosin subfragment 2 or S-2, and a C-terminal light meromyosin (LMM). When light meromyosin is cut away from the myosin molecule, the two-headed structure remaining is known as heavy meromyosin (HMM). The places at which the proteases cut are regions of flexibility in the original structure. Specifically, the heads can rotate about the arms, and there is a region of flexibility about 40 nm from the head-rod junction. Light meromyosin and any structure containing light meromyosin are insoluble in intracellular fluid, but all other segments are readily soluble.

7 of 12 6/13/17, 6:55 AM Muscle - AccessScience from McGraw-Hill Education http://www.accessscience.com/content/muscle/439700 Myosin molecules are assembled into a thick filament so that there is a central core of strongly interacting, insoluble light meromyosin segments with radially protruding soluble heavy meromyosin portions. Thus the central core is devoid of radiating heavy meromyosin and the S-1 moieties are situated adjacent to the actin filaments (Fig. 6). In the electron microscope the heavy meromyosin moieties appear as projections issuing from the thick filaments which occasionally touch adjacent actin filaments. These projections have been called cross-bridges. A cross-bridge is mainly an S-1 moiety, perhaps with some contribution from the S-2.

Fig. 6 Diagram of the molecules in a plane of nearest actin-myosin couples. The second S-1 of each is shown in limited fashion; each would be nearest to a separate actin filament. There is approximately one myosin head to every five actins.

Fueling reaction

It is widely accepted that the hydrolysis of ATP (or its analogs) is the fueling reaction for a great variety of biological machines, including muscle. There are, however, four aspects of this reaction that are especially important in the present + context. First, the participants, in this reaction ATP, ADP, and Pi , are highly ionic. Each interacts strongly with both H and Mg2+. This means that the free energy obtainable from the reaction depends on these ionic concentrations. Second, the reaction does not proceed at an appreciable rate in the absence of catalysis, or even in the presence of the catalyst myosin. It proceeds rapidly only when both actin and myosin are present in the catalytic form, actomyosin. These circumstances ensure that fuel is degraded only when work is being performed. Third, enzymatic catalysis always proceeds in steps, so the free energy is dissipated in steps. The algebraic sum of these stepwise decrements must equal the total free energy of the ATP hydrolysis, but the pattern of the steps is characteristic of the particular enzyme. Fourth, the steady-state concentration of MgATP in muscle is around 3 millimolar. The MgATP would be quickly exhausted in heavy exertion were it not that the

breakdown products, ADP and P i , are swiftly synthesized back into ATP by the system (at the expense of creatine phosphate), and more slowly but more extensively synthesized by the glycolytic system (at the expense of stored glycogen) and by mitochondria (at the expense of oxygen and foodstuffs).

Physiology

Under experimental conditions (when the membrane of a muscle fiber has been removed), the chemical composition of the fluid bathing the contractile apparatus can be controlled. It is then possible to correlate unambiguously the composition and the physiological state of a muscle fiber. The results are as follows: (1) When the medium is devoid of ATP, as in exhaustion or death, the fiber is stiff and inextensible, and is said to be in rigor. This physiological state arises because in the absence of ATP the erstwhile high affinity of the S-1 moieties for the actins literally bonds all the cross-bridges to adjacent actins. (2) When the medium contains Mg2+ and ATP but no Ca2+ , the fiber is flaccid and unresistingly extensible; it is then said to be relaxed. This state comes about because the calcium sensor is preventing any interaction between the cross-bridges and the adjacent actins. (3) When the muscle medium contains Mg 2+, ATP, and Ca2+ , the fiber is active. If it is prevented from shortening (isometric), it is developing tension and consuming ATP at a low rate; and if it is not restrained (isotonic), it is shortening while at the same time consuming ATP at a rate dependent on the speed of shortening. It is thought that, under these circumstances, force interactions tending to produce the filament interdigitation are going on between the cross-bridges and the adjacent actins.

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The calcium sensor serves as a regulator of muscle action. Along the two grooves of the actin helix in every thin filament, firmly attached to actin, are deployed two long chains of a protein called . Periodically along each tropomyosin strand are clumps of globular proteins called (T, I, and C). There is reason to think that such clumps are attached to both tropomyosin and actin. C contains several Ca 2+ binding sites, two of which have a very strong affinity for the Ca2+ and strongly prefer it to Mg 2+. These sites fit the sensor role.

Experimentation with certain of the Ca 2+-binding proteins led to what seemed a well-documented theory of Ca2+ regulation in vertebrate skeletal muscle. In relaxation, along its helical course, tropomyosin is bound to actin monomers so that it masks all their S-1 binding sites, thus blocking all contractile activity. As the Ca2+ concentration in the bulk interfibrial solution rises (this Ca2+ concentration is itself regulated by the sarcoplasmic reticulum), it binds to the troponins which then tilt so as to pull the masks off the actins, thus permitting contraction. There is reason to think that, while elements of this theory remain correct for vertebrate skeletal muscle, other tissues may have other operative components in the Ca 2+ sensing system. It has been found, for example, that in mollusks, Ca2+ sensing is performed solely by the light chains, tropomyosin/troponin being unnecessary. There is mounting evidence that something of the same myosin-linked mechanism operates in vertebrate smooth muscle. Even in vertebrate skeletal muscle the discovery that the light chains must be intact for regulation to occur suggests that these elements work in parallel with tropomyosin/troponin. Evidence has also appeared that not only physical separation of the myosin and actin but also some other means of myosin ATPase inhibition bring about relaxation. Finally, whether and how the Ca 2+-binding site of actin has a role in the actin-activation of ATPase remains to be discovered. Perhaps if it does, it too will have a role in regulation. At the present time the field of Ca 2+ regulation has a surfeit of proposed mechanisms.

Length–tension relationship

The explanation of the active state discussed above arises from a classical physiological experiment known as the length– tension relationship. When the sarcomere is at rest length, every cross-bridge in a plane of nearest actins and myosins has access to actin. This continues to be so for small extensions of the fiber and its sarcomeres. But with increasing stretch a length is reached at which this ceases to be so. For stretches beyond this critical length the number of cross-bridges with adjacent actin decreases in proportion to stretch. At high extensions a second critical length is reached beyond which no cross-bridges have adjacent actins. In the experiment, the fiber, in the relaxed state, is drawn out to the desired length and clamped, then ambient condition (3) above is imposed to activate it (in the case of a membranated fiber, electrical excitation accomplishes the same condition). Two quantities are measured at each fixed length: the static tension developed against the length clamp and the ATPase activity. These two quantities, along with the number of cross-bridges opposite to actins, are then plotted against extension (Fig. 7). The graphs are surprisingly similar: flat at first, then falling linearly, finally flat at zero. These results strongly suggest that the ATPase-driven force generators are the cross-bridge–actin couples.

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Fig. 7 Sketch of how either tension- or actin-activated ATPase depends on sarcomere length. Letters correspond to sarcomere length in Fig. 4. The correspondence is the basis for thinking that the force-generating unit is a myosin S-1 and its associated actin.

The previous experiment shows that the total force generated by the fiber is simply the sum of the unitary forces generated by a fixed number of cross-bridge–actin couples, but because of clamping, no shortening was permitted. When shortening occurs, the number of couples that can interact can still be kept approximately constant by limiting the experiment to small (around 10%) contractions, but even so a new phenomenon enters, since time changes the relative position of a particular cross-bridge and a particular actin. In this investigation the fiber is allowed to shorten against a constant external force (f) that it can overcome, such as a light weight (force = mass × gravitational acceleration), and the velocity of shortening (υ) is measured. The empirical result is the characteristic equation of isotonic contraction: (f + a)υ = where f = force (load); υ = velocity; load; and a,b = constants. The arguments are now more complicated, but this behavior too can be rationalized by assumptions as to how the force interaction between a couple depends on time and distance.

Energy transformation

The structural-functional interpretation of the length–tension diagram (above) suggests that a myosin S-1 piece (attached to the thick filament) reacting with an actin monomer (attached to the thin filament) is the unitary engine causing the interfilament slide (Fig. 8). The S-1 piece binds actin through its A site and catalyzes ATPase at its N site (Fig. 9). The intermediates in the breakdown of ATP appear sequentially on the N site: first x, then y, then z, and so on. When one ATP is totally degraded, then a fresh ATP initiates the next sequence (x, y, z, and so on). Enzymatic activity is cyclic. Because of the way that S-1 is built, it seems that to each intermediate there corresponds a specific way of holding actin at the A site, namely, in position x, in position y, and so on. Thus, corresponding to endlessly repeated ATPase cycles there are endlessly repeated cycles in the manner of holding actin, that is, mechanical cycles. Each mechanical cycle constitutes a force impulse. When the enzymatic and mechanical activity of all the S-1 pieces acting in concert is summed, a steady force is maintained at the cost of steady ATP hydrolysis. Ultimately, therefore, the energy transduction in muscle is carried out by the molecular structures of the S-1 pieces of myosin.

Fig. 8 Diagram suggesting that shortening would result if actin and an S-1 moiety could bind at two different angles.

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Fig. 9 The hypothesized mechanism of the transformation of chemical energy into mechanical energy in muscle. N is the enzymatic site that catalyzes the hydrolysis of ATP; A is the site at which actin binds; x and y are successive intermediates in ATP hydrolysis. When x is occupying N, the actin binds at position x on the A site; when y is occupying N, the A site binds actin at position y. During catalysis, when x is chemically converted into y, actin is caused to move from one binding position to another. This movement is forced by the chemical conversion, so the product of the distance moved and the force constitutes mechanical work.

Patricia Rainford

Links to Primary Literature

R. M. Santaella et al., The effect of α1-adrenergic antagonist tamsulosin (flomax) on dilator smooth muscle anatomy, Ophthalmology, 117(9):1743–1749, 2010 DOI: https://doi.org/10.1016/j.ophtha.2010.01.022 (https://doi.org/10.1016 /j.ophtha.2010.01.022)

Additional Readings

C. Emerson et al., Molecular of Muscle Development, 1986

A. Engle and C. Franzini-Armstrong, Myology, 2 vols., 2d ed., 1994

G. H. Pollack, Muscles and Molecules: Uncovering the Principles of Biological Motion, 1990

D. J. Schneck, The Mechanics of Muscle, 1992

R. J. Stone and J. A. Stone, Atlas of the Skeletal Muscles, 3d ed., 1999

D. E. Rassier (ed.), Muscle Biophysics: From Molecules to Cells, Springer Science+Business Media, New York, 2010

B. A. Wood and R. Diogo, Comparative Anatomy and Phylogeny of Primate Muscles and Human Evolution, CRC Press, Boca Raton, FL, 2012

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