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7.1 Introduction

One of the distinguishing characteristics of animals is their ability to use coordinated movement to explore their environ­ment. For large multicellular animals this movement is achieved by the use of muscles, which consist of cells that can change their length by a specific contractile process. Such cells are known as myocytes. In vertebrates, including humans, three types of muscle can be identified on the basis of their structure and function: skeletal muscle, cardiac muscle, and smooth muscle. As the name implies, skeletal muscle is the muscle attached

Fig. 7.1 The microscopical appearance of skeletal, cardiac, and smooth muscle.

directly to the bones of the skeleton and its role is both to main­tain posture and to move the limbs by contracting. Cardiac muscle is the muscle of the heart, and smooth muscle is the muscle that lines the blood vessels and the hollow organs of the body. Together the thtee kinds of muscle account for nearly 50 per cent of body weight, the bulk of which is contributed by skeletal muscle (about 40 per cent of total body weight).

When skeletal and cardiac muscle are viewed by microscopy their cells are seen to have characteristic striations—small regular stripes running across the individual muscle cells. For this reason they are sometimes called striated muscles. Smooth muscle lacks the striations seen in skeletal and cardiac muscle and consists of sheets of spindle-shaped cells. The microscopical appearance of the different kinds of muscle is shown in Fig. 7.1. Despite these diffetences in structure, the molecular basis of the contractile process is very similar for all types of muscle.

This chapter is concerned chiefly with the physiological properties of the different kinds of muscle. It will also outline the cellular and molecular basis of the conttactile process itself.

7.2 The structure of skeletal and cardiac muscle

Skeletal muscle

Each skeletal muscle is made up of a number of individual muscle fibers, which are grouped together in bundles called fasciculi. The muscle fibers are bound together by a coat of connective tissue called the epimysium. Connective tissue also lies within the body of a muscle and is essential for the transmission of the mechan­ical force generated by the muscle to the skeleton. The skeletal muscle fibers are long, thin, cylindrical cells that contain many nuclei. They may be up to 30 cm in length and are usually 10-100 /xm in diameter. Nevertheless, few muscle fibers extend for the full length of a muscle. Individual muscle fibers are made up of filamentous bundles that run along the length of the fiber. These bundles are called myofibrils and have a diameter of 1—2 /Am. Each myofibril consists of a repeating unit known as a sarcomere and it is the alignment of the sarcomeres between adjacent myofibrils that gives rise to the characteristic striations of skeletal muscle. The structute of skeletal muscle is sum­marized in Fig. 7.2.


7 Muscle

Fig. 7.2 The organization of skeletal muscle at various degrees of magnification. A shows the appearance of the whole muscle; B, the appearance of a muscle fasciculus; C, the appearance of a single muscle fiber; D, the structure of individual myofibrils; E, the appearance of the protein filaments that make up the individual sarcomeres; and F, the organization of actin and myosin in the thin and thick filaments.

The sarcomere is the fundamental contractile unit within skeletal and cardiac muscle. Each sarcomere is only about 2 μm in length so that each myofibril is made up of many sarcomeres. When a muscle fiber is viewed by polarized light the sarcomeres are seen as alternating dark and light zones. The regions that appear dark do so because they refract the polarized light. This property is called anisotropy and the corresponding band is known as an A band. The light regions do not refract polarized light and are said to be isotropic. These regions are called / bands. Each I band is divided by a characteristic line known as a Z line and the unit between successive Z lines is a sarcomere. At high magnification in the electron microscope the A bands are seen to be composed of thick filaments arranged in a regular order. The I bands consist of thin filaments. The principal protein of the A bands is myosin, while that of the I bands is actin. The interaction between these proteins is fundamental to the contractile process (Section 7.4).

Like all cells, muscle cells are bounded by a cell membrane, known as the sarcolemma. Beneath the sarcolemma lie the nuclei

Fig. 7.3 The detailed organization of the T-system and sarcoplasmic reticulum of skeletal muscle. Note the origin of the T-tubules at the plasma membrane (sarcolemma) and the close apposition of the T-tubules and the terminal cisternae of the sarcoplasmic reticulum to form the triads. The arrangement of the T-tubules shown is that found in amphibians. In mammals the T-Tubules traverse the fibre at the junction of the A and I bands.

and many mitochondria. In mammalian muscle, narrow tubes run from the sarcolemma across the fibre at the junction of the A and I bands. These tubules are known as T-tubules. Each myofibril is surrounded by the sarcoplasmic reticulum, a mem­branous structure that is homologous with the endoplasmic reticulum of other cell types. Where the T-tubules and the sar­coplasmic reticulum come into contact, the sarcoplasmic reticu­lum is enlarged to form the terminal cisternae. As a result of this arrangement, each T-tubule is in close contact with the cisternae of two sarcomeres and the whole complex is called a triad (Fig. 7.3). The T-tubules and triads play an important role in excita­tion-contraction coupling (see Section 7.4).

Cardiac muscle

Cardiac muscle consists of individual cells linked together by junctions called intercalated disks. Characteristically the inter­calated disks cross the muscle in irregular lines. Individual cardiac muscle cells are aligned so that they run in arrays that often branch to link adjacent groups of fibers together. The indi­vidual cells are about 15 ^m in diameter and up to 100 /xm in length and are coupled together by gap junctions. This permits electrical activity to spread from one cell to another. The cells usually have only one centrally located nucleus. Cardiac muscle cells (also called cardiac myocytes) contain large numbers of mito-

7.3 How does a skeletal muscle contract?


Fig. 7.4 The appearance of cardiac muscle at high magnification. The field of view shows two myocytes joined by an intercalated disk which courses irregularly across the lower part of the field. Note the close apposition of the plasma membrane at the gap junctions, the large numbers of mitochondria and the irregular arrangement of the Z lines.

chondria distributed throughout the cytoplasm (Fig. 7.4). The structure of the contractile elements of cardiac myocytes is very similar to that of skeletal muscle, but the individual sarcomeres are not as regularly arranged. The myocytes also contain T-tubules and sarcoplasmic reticulum, but the arrangement is less ordered than that seen in skeletal muscle. Usually one T-tubule is associated with one sarcoplasmic cisterna to form a diad.


  1. Skeletal muscle is made up of long, cylindrical, multi-nucleated cells,
    called muscle fibers. Muscle fibers contain myofibrils, which are made
    up of repeating units called sarcomeres. The sarcomeres are the
    fundamental contractile units. Each sarcomere is separated from its
    neighbors by Z lines and consists of two half I-bands, one at each
    end, separated by a central A band. The myofibrils are surrounded by
    a membranous structure known as the sarcoplasmic reticulum.

  2. Cardiac muscle is made up of many individual cells (cardiac
    myocytes) linked together via intercalated disks. Unlike skeletal
    muscle, cardiac myocytes generally have a single nucleus. The
    striated appearance of cardiac myocytes is due to the presence of an
    orderly array of sarcomeres, similar to that seen in skeletal muscle.

3. The principal contractile proteins of the sarcomeres of both skeletal
and cardiac muscle are actin and myosin.

^ 7.3 How does a skeletal muscle contract?

Skeletal muscle, like nerve, is an excitable tissue and stimulation of a muscle fiber at one point will lead to excitation of the whole

cell. In the body a motor unit is activated by an impulse in its motor nerve. This leads to the excitation of the individual muscle fibers of that motor unit via the generation of a motor end-plate potential (epp), as described in Chapter 6. The epp depolarizes the muscle fiber membrane in the region adjacent to the end-plate and this depolarization, in its turn, triggers an action potential that propagates away from the end-plate along the whole length of the muscle fiber. The passage of the muscle action potential is followed by contraction of the muscle fiber and the development of tension. The process by which a muscle action potential triggers a contraction is known as excitation-contraction coupling.

What steps link the muscle action potential to the contractile response? It has been known for a long time that injection of calcium into a muscle fiber causes it to contract. It was later discovered that significant amounts of calcium are stored in the sarcoplasmic reticulum and that this calcium is released during contraction. It is now thought that the depolarization of the plasma membrane during the muscle action potential spreads along the T-tubules where it causes calcium channels in the sarcoplasmic reticulum to open. As a result, calcium stored in the sarcoplasmic reticulum is released and the level of calcium in the sarcoplasm rises. It is this rise in calcium that triggers the contraction of the muscle fiber. Relaxation of the muscle occurs as the calcium in the sarcoplasm is pumped back into the

Fig. 7.5 Flow diagram to illustrate the sequence of events leading to the contraction and subsequent relaxation of a skeletal muscle fiber


7 Muscle

sarcoplasmic reticulum by a calcium pump of the kind described in Chapter 4. These events are summarized in Fig. 7.5.

How is tension generated and how does a rise in calcium lead to the contractile response? All muscles contain two proteins— actin and myosin. In skeletal and cardiac muscle the thick filaments are composed chiefly of myosin while the thin filaments contain actin (the principal protein) and lesser quan­tities of two other proteins, known as troponin and tropomyosin. Muscle contraction is now known to occur through interactions between actin and myosin which result in the thick and thin filaments sliding past each other. This is known as the sliding filament hypothesis of muscle contraction.

The individual myosin molecules of the thick filaments are arranged so that the thin tail regions associate together to form

Fig. 7.6 A schematic representation of the molecular events responsible for the relative movement of the thin and thick filaments of a striated muscle. (Based on Rayment et al. (1993). Science, 261, 50-8.)

the backbone of the thick filaments while the thicker head region projects outwards to form cross-bridges with the neigh­boring thin filaments (Fig. 7.2e, f). Each actin molecule is able to bind one myosin head. The two molecules dissociate when a molecule of ATP is bound by the myosin. The subsequent hydrolysis of the ATP causes a change in the angle of the head region of the myosin molecule that enables it to move to the next actin molecule and bind once more. The release of the inorganic phosphate leads to a change in the angle of the head group resulting in the generation of force (Fig. 7.6). Once again, ATP causes the dissociation between the actin and myosin and the cycle is repeated. As a result, the myosin heads effectively walk along the thin filament and the thick and thin filaments slide past each other, so shortening the fiber.

The role of calcium in muscle contraction

If purified actin and myosin are mixed in a test tube they form a gel (a jelly-like mixture). If ATP is then added to this mixture it contracts and the ATP is hydrolyzed. What prevents actin and myosin continuously hydrolyzing ATP in an intact muscle fiber? The answer to this problem came when it was discovered that muscle contained two other proteins, called troponin and tropomyosin. These proteins form a complex with actin that pre­vents it binding the myosin head groups. When calcium is released from the sarcoplasmic reticulum, the free calcium in the

Fig. 7.7 The sliding filament theory of muscle contraction and the length-tension relationship of skeletal muscle. The sequence A-D represents the force developed as the resting fiber length is increased. When the thin and thick filaments fully overlap and the A band is compressed against the Z line (point A) the muscle is unable to develop tension. As the muscle is stretched so that the thin and thick filaments overlap without compressing the A band, active tension is generated when the muscle is stimulated (point B). Further stretching provides optimal overlap between the thin and thick filaments, leading to maximal development of tension (point C). If the muscle is stretched to such a degree that the thin and thick filaments no longer overlap there is no tension developed (point D).

^ 7.4 The activation and mechanical properties of skeletal muscle


sarcoplasm is transiently taised from the low levels found in resting muscle (0.1—0.2 /xM) to a peak value of about 10 μM at the beginning of a contraction. The troponin complex binds the released calcium and, in doing so, it changes its position on the actin molecule so that actin and the myosin head groups can interact as described above.

The sliding filament theory of muscle contraction provides a clear explanation for the length—tension relationship (Fig. 7.7). When the muscle is at its natural resting state, the thin and thick filaments overlap fully and the maximum number of cross-bridges are formed. When the muscle is stretched, the degree of overlap between the thin and the thick filaments is reduced and the number of cross-bridges falls. This leads to a decline in the ability of the muscle to genetate tension. When the muscle is shotter than its natural resting length, the thin filaments already fully overlap the thick filaments but the filaments from each end of the sarcomere touch in the center of the A band and each interferes with the motion of the other. As a result, tension development declines. When the thin and thick filaments fully overlap, the A bands abut the Z lines and tension development is no longer possible.

The energy for contraction is derived from the hydrolysis of ATP. As with other tissues, this is derived from the oxidative metabolism of glucose and fats (Chapter 3). However, during the contractile cycle it is important for the levels of ATP to be main­tained. Since the blood flow through a muscle during con­traction may be intermittent, a store of high-potential phosphate is needed to maintain contraction as the available ATP (about 3 mM) would all be hydrolyzed within a few seconds. This need is met by creatine phosphate (also known as phosphocreatine) which is present in muscle at high concentrations (about 15-20 mM) and has a phosphate group that is readily transferred to ATP. This reaction is catalyzed by the enzyme creatine kinase:

globin and have relatively few mitochondria but have high con­centrations of glycolytic enzymes. They are well adapted to provide periods of tension development during anaerobic exer­cise but, as the stores of glycogen are used up, their lactate levels rise, their pH falls, and they become fatigued. In contrast, slow-twitch muscle fibers have many more mitochondria and contain large quantities of myoglobin. They have a highet capillary density and are adapted for long periods of aerobic activity. Consequently they do not normally accumulate lactate and have a higher resistance to fatigue.


  1. The link between the electrical activity of a muscle and the contrac­
    tile response is called excitation-contraction coupling. The action
    potential of the sarcolemma depolarizes the T-tubules and this causes
    calcium channels in the sarcoplasmic reticulum to open. This leads to
    an increase in calcium around the myofibrils and the development of

  2. The A band of each sarcomere consists mainly of myosin molecules
    arranged in thick filaments and the I band consists mainly of actin,
    tropomyosin, and troponin arranged in thin filaments. Tension devel­
    opment occurs when actin and myosin interact. This can only occur
    when the troponin complex binds calcium. During contraction the
    actin and myosin form a series of cross-bridges that break and reform
    as ATP is hydrolyzed. As a result, the thick and thin filaments slide
    past each other and force is generated.

  3. The energy for muscle contraction is provided by the breakdown of
    ATP. Initially this is derived from the resting stores and from creatine
    phosphate but, in prolonged exercise, the ATP for muscle contraction
    is derived either from glycogen breakdown to lactate (anaerobic activ­
    ity) or from the oxidative metabolism of glucose and fats (aerobic
    activity). During phases of anaerobic activity, muscles accumulate
    lactate and hydrogen ions and this contributes to muscular fatigue.

creatine phosphate + ADP + H+

creatine + ATP

Muscle fatigue in twitch muscles is

associated with an accumulation of lactate

and a fall in muscle pH

During heavy exercise insufficient oxygen may be delivered to the exercising muscles. In this situation, ATP is generated from glucose via the glycolytic pathway. This anaerobic phase of muscle contraction is much less efficient in generating ATP (Chapter 3) and both lactate and hydrogen ions are produced in increasing quantities. As these ions accumulate, muscle pH falls and the muscular effort becomes progressively weaker. This is known as fatigue. During muscle fatigue the muscle and motor nerve remain able to propagate action potentials but the ability to develop tension is impaired.

Different types of muscle fiber show different susceptibility to fatigue. Fast-twitch fibets develop great tension rapidly and contain large quantities of glycogen. They contain little myo-

^ 7.4 The activation and mechanical properties of skeletal muscle

Under normal circumstances a skeletal muscle will only contract when the motot nerve to the muscle is activated. The signal to cause contraction of a skeletal muscle therefore originates in the CNS and the resulting contraction is said to be neurogenic in origin. In contrast, catdiac muscle contracts spontaneously, even when isolated from the body, as long as it is placed in a suitable nutrient medium. Some smooth muscles behave in the same way. Contractions that arise from activity within the muscle itself are said to be myogenic in origin.

The innervation of skeletal muscles

The motor nerves supplying a mammalian skeletal muscle are myelinated. As the nerve enters the muscle it branches, and the individual axons also branch, so that one motor axon makes contact with a number of muscle fibers. A motot axon and its


7 Muscle

100 N

40 ms


associated muscle fibers are called a motor unit. When a motor axon is activated all the muscle fibers it supplies contract in an 'all or none' fashion. The size of motor units varies from muscle to muscle according to the degree of control required. Where fine control is not required the motor units are large. Thus, in the gastrocnemius muscle of the calf, a motor unit may contain up to 2000 muscle fibers. In contrast, the motor units of the extraocular muscles (which control the direction of the gaze) are much smaller (perhaps as few as 6-10 muscle fibers being supplied by a single motor nerve).

The detailed mechanism by which a motor nerve activates a skeletal muscle fiber (neuromuscular transmission) has already been considered in Section 6.5.

The mechanical properties of skeletal muscle

Like nerve, skeletal muscle is an excitable tissue that can be activated by direct electrical stimulation. When a muscle is activated, it shortens and, in doing so, exerts a force on the tendons to which it is attached. The amount of force exerted depends on many factors:

  1. the number of active muscle fibers;

  2. the frequency of stimulation;

  3. the rate at which the muscle shortens;

  4. the initial resting length of the muscle; and

  5. the cross-sectional area of the muscle.

The role of these different factors will now be considered.

Consider first the situation where the muscle is being activ­ated artificially by a single electrical shock to its motor nerve. It should be clear that if few motor fibers are activated by the elec­trical stimulus, only a small proportion of the muscle fibers will contract to generate tension. If the intensity of the stimulus is increased, more motor fibers will be recruited and there will be a corresponding increase in the total tension developed. When all the motor units are activated, total tension developed will reach its maximum. This stimulus is called a maximal stimulus. The response of a muscle to a single stimulus is called a muscle twitch and the tension developed is called the twitch tension.

Muscles do not elongate when they relax unless they are stretched. In the body this stretching is achieved for skeletal muscles by the arrangement of muscle pairs acting on particular joints. These pairs of muscles are known as antagonists. In cardiac muscle the blood returning to the heart performs the stretching action.

The force developed by a muscle increases during repetitive activation

When a muscle fiber is activated, the process of contraction begins with an action potential passing along its length. This is followed by the contractile response, which consists of an initial phase of acceleration during which the tension in the muscle

Fig. 7.8 The time course of the contractile response and action potential of a fast (twitch) skeletal muscle. Note that (1) the contractile response begins as the action potential is ending and (2) force is expressed as Newtons (N).

increases until it equals that of the load to which it is attached and then the fiber begins to shorten. This is followed by a period during which the fiber shortens at a relatively constant rate. As the muscle contracts, the rate of shortening progressively falls— the phase of decelerarion. Finally, the muscle relaxes and the tension it exerts declines to zero. The whole cycle of shortening and relaxation takes several tens of milliseconds, while the muscle action potential is over in a matter of 2 or 3 ms. Con­sequently, the mechanical response greatly outlasts the electrical signal that initiated it (Fig. 7.8).

If a muscle is activated by a pair of stimuli that are so close together that the second stimulus arrives before the muscle has fully relaxed after the first, the total tension developed following the second stimulus is greater than that developed in response to a single stimulus. This increase in developed tension is called summation and is illustrated in Fig. 7.9a and b. The degree of summation is at its maximum with short intervals and declines as the interstimulus interval increases. If a number of stimuli are given in quick succession, the tension developed progressively summates. This response is called a tetanus. At low frequencies, the tension oscillates at the frequency of stimulation, as shown in Fig. 7.9c but, as the frequency of stimulation rises, the development of tension proceeds more and more smoothly. When tension develops smoothly (Fig. 7.9d), the contracture is known as a fused tetanus.

Why is a muscle able to develop more tension when two or more stimuli are given in rapid succession?

Consider first how tension develops during a single twitch. When the muscle is acrivated it must transmir the tension developed to the load. To do this the tension of the tendons and of the connective tissue of the muscle itself must be raised to that of the load. As the tendons are to some degree elastic, they need to be stretched a little until the tension they exert on the load is equal to that of the muscle. This takes a short, but finite, amount of time during which the response of the tension-generating machinery begins to decline. The transmission of

7.4 The activation and mechanical properties of skeletal muscle


Fig. 7.9 The summation and fusion of the mechanical response of a muscle in response to repetitive stimulation, (a) The response to a single electrical stimulus (arrow), (b) The summation of tension when a second stimulus (S2) is given before the mechanical response to the first has decayed, (c) The summation of tension during a brief train of stimuli, (d) The smooth development of tension during a high-frequency train of stimuli (giving a fused tetanus). Note the different time and tension calibrations for (a) and (b) compared to (c) and (d).

force to the load is accordingly reduced in efficiency. This also accounts for the initial acceleration in the rate of contraction described above. During a train of impulses, however, the con­tractile machinery is activated repeatedly and the tension in the tendons has little time to decay between successive contractions. Transmission of tension to the load is more efficient and a greater tension developed. Furthermore, when stimuli are given in rapid succession, the contractile machinery will be primed because not all the calcium released during one stimulus will have been pumped back into the sarcoplasmic reticulum before the arrival of the next.

Broadly speaking, skeletal muscle fibers can be classified as fast or slow, according to their rate of contraction. Most muscles contain a mixture of both kinds of fiber but some have a predominance of one type. Fast muscles shorten at about 40—45 mm s"1 and relax relatively quickly. Slow muscles con­tract at about 15 mm s_1 and relax slowly. The two types can also be distinguished by their structure and composition. Fast muscle fibers have few mitochondria and are white in appearance as they have little myoglobin (an oxygen-binding protein, see Chapter 13). Slow muscle fibers, which play an important role in the maintenance of posture, are rich in both mitochondria and myoglobin, which gives them a reddish appearance.

Smooth tension development in intact

muscle is due to asynchronous activation

of motor units

In the absence of organic disease, the development of tension during normal movement is smooth and progressive. This arises because motoneurons are recruited progressively by the CNS. Consequently, the motor units comprising the muscle are activated at different times—very unlike the experimental situ­ations described in the previous sections. Individual motor units may be activated by relatively low frequencies of stimulation but the maintenance of a steady tension ensutes the efficient trans­mission of force to the load. The ability of a muscle to maintain a smooth contraction is further enhanced by the presence of both fast and slow muscle fibers in most muscles.

The power of a muscle depends on the rate at which it shortens

The tate at which a muscle shortens depends on the load on which it acts. If there is no external load, a muscle shortens at its maximum rate. With progressively greater loads the rate of shortening decreases until the load is too great for the muscle to

Fig. 7.10 The force—velocity relation for a skeletal muscle. Note that maximum force is developed during an isometric contraction but maximum speed of shortening occurs in an unloaded muscle. Maximum power is developed when the muscle shortens at about one-third of maximum velocity.

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