Functions of Skeletal Muscle

Although locomotion is the primary function of skeletal muscle tissue, the muscular system also performs other important roles. In addition to locomotion and manipulation, skeletal muscles maintain body posture, assist in venous return of blood to the heart, and play an important role in thermogenesis (heat generation). Heat is a by-product of cellular respiration; and because muscles use a great deal of energy for movement, they also generate a great deal of heat. Additionally, muscles act as energy transducers by converting biochemical energy from ingested food into mechanical and thermal energy. Skeletal muscles also protect internal organs and make up most of the protein in the body. Because muscles represent such a large amount of protein, they constitute a potential but rarely used form of stored energy. The use of protein as an energy substrate is discussed in Chapter 3.

Characteristics of Muscle Tissue

Muscle tissue has unique characteristics that are specifically suited to its primary function, namely, converting an electrical signal (action potential [AP]) into a mechanical event (contraction of muscle fibers). The characteristics that allow a muscle to produce movement include irritability, contractility, extensibility, and elasticity. Irritability refers to the ability of a muscle to receive and respond to stimuli. The stimulus is generally in the form of a chemical message (from a neurotransmitter), and the response is the generation of an electrical current (AP) along the cell membrane. Contractility refers to the ability of a muscle to respond to a stimulus by shortening, which produces force. Extensibility refers to the ability of a muscle to be stretched or lengthened. Stretching occurs when a muscle is manipulated by external force. Elasticity refers to the ability of a muscle to return to its resting length after being stretched. These characteristics of muscles function together to allow for human movement.

Organization and Connective Tissue

Skeletal muscles are organized in a systematic fashion, as depicted in Figure 2-2. Some of this organization is apparent to the naked eye, but other aspects are apparent only when muscle fibers are viewed through a simple or an electron microscope.

Figure 2-2 Organization of skeletal tissue. A, Intact skeletal muscle. Biceps brachii are attached to bones through tendons. B, Connective tissue. The entire muscle is surrounded by connective tissue called epimysium. The muscle is organized into bundles called fasciculi, which are surrounded by connective tissue called perimysium. Each fasciculus contains many individual fibers surrounded by connective tissue called endomysium.

(From Plowman SA, Smith DL: Exercise physiology for health, fitness, and performance, ed 2, San Francisco, 2003, Benjamin Cummings.)

Skeletal muscles are attached to bones by tendons, an arrangement that allows the contraction of a muscle to move a bone. Each muscle is bound together by a thick layer (sheath) of connective tissue called fascia. Just beneath the fascia is a more delicate layer of connective tissue called epimysium that directly covers the muscle.

The interior of the muscle is subdivided into bundles of muscle fibers called fasciculi (the singular is fasciculus or fascicle), which are also surrounded by connective tissue. The sheath of connective tissue that separates the fasciculi within a skeletal muscle is called perimysium. The fasciculi are composed of many individual muscle fibers (cells), each of which is surrounded by its own sheath of connective tissue called endomysium. The three layers of connective tissue (epimysium, perimysium, and endomysium) provide the framework that holds the muscle together. These three layers of connective tissue come together at each end of the muscle to form the tendons that attach the muscle to bone. As a muscle contracts, it pulls on the connective tissue in which it is wrapped, causing the tendon to move the bone to which it is attached.

Architectural Organizations

Different arrangements of fasciculi within a muscle account for the different shapes that a muscle may take. Muscles can be described as longitudinal, fusiform, radiate, unipennate, bipennate, or circular, as shown in Figure 2-3. The shape of the muscle determines its range of motion and influences its power production. The longer and more parallel muscle fibers, as found in longitudinal muscles, allow for greater muscle shortening. Bipennate and multipennate muscles, by contrast, shorten little but are more powerful.

Figure 2-3 Arrangement of fasciculi.

(From Plowman SA, Smith DL: Exercise physiology for health, fitness, and performance, ed 2, San Francisco, 2003, Benjamin Cummings.)

Sarcoplasmic Reticulum and Transverse Tubules

Figure 2-4 illustrates the relationship among the myofibrils, sarcoplasmic reticulum, and transverse tubules. The sarcoplasmic reticulum (SR), a specialized organelle that stores and releases calcium, is an interconnecting network of tubules running parallel with and wrapped around the myofibrils. (Note: in the figure the sarcolemma has been partially removed in order to illustrate the SR and myofibrils.) The major significance of the sarcoplasmic reticulum is its ability to store, release, and take up calcium and thereby control muscle contraction. Calcium is stored in the portion of the sarcoplasmic reticulum called the lateral sacs or cisterns.

The transverse tubules (T tubules) are organelles that carry the electrical signal (AP) from the sarcolemma to the interior of the cell. T tubules are continuous with the sarcolemma and protrude into the sarcoplasm of the cell. Although the T tubules run in close proximity to the sarcoplasmic reticulum and interact with it, they are anatomically separate organelles. As the name implies, the T tubules run perpendicular (transverse) to the myofibril. The spread of an electrical signal through the T tubules causes the release of calcium from the lateral sacs of the sarcoplasmic reticulum.

Myofibrils and Myofilaments

Each muscle fiber contains hundreds to thousands of smaller cylindrical units, or rodlike strands, called myofibrils (see Figure 2-4). Myofibrils are contractile structures composed of myofilaments. These myofibrils, or simply fibrils, typically lie parallel to the long axis of the muscle cell and extend the entire length of the cell. Myofibrils account for approximately 80% of the volume of a muscle fiber and are composed of two myofilaments (thick and thin myofilaments). Each repeating unit along the myofibril is referred to as a sarcomere.

Sarcomeres

A sarcomere is the functional unit (contractile unit) of a muscle fiber. As illustrated in Figure 2-5, each sarcomere contains two types of myofilaments: thick filaments, composed primarily of the contractile protein myosin, and thin filaments, composed primarily of the contractile protein actin. Thin filaments also contain the regulatory proteins, troponin and tropomyosin. When myofilaments are viewed under an electron microscope, their arrangement gives the appearance of alternating bands of light and dark striations. The light bands are called I bands and contain only thin filaments. The dark bands are called A bands and contain thick and thin filaments, with the thick filaments running the entire length of the A band. Thus the length of the thick filament determines the length of the A band.

Figure 2-5 Arrangement of myofilaments in a sarcomere. A, Micrograph of sarcomeres. B, Model of sarcomeres. C, Relationship between thick and thin filaments. D, Cross-sectional view of thin filaments. E, Cross-sectional view of thick filaments. F, Cross-sectional view of thick and thin filaments.

(From Plowman SA, Smith DL: Exercise physiology for health, fitness, and performance, ed 2, San Francisco, 2003, Benjamin Cummings.)

The names for the various regions of the sarcomere are not arbitrary; they are derived from the first letter of the German word that describes their appearance. The names for the bands describe the refraction of light through the respective bands. The I band is abbreviated from the word isotropic, which means that this area appears lighter because more light can pass through it. The A band is so named because of its anisotropic properties, meaning that it appears darker because it does not allow as much light to pass through. These properties are directly related to the type of filament present.

Each A band is interrupted in the midsection by an H zone (from the German Hellerscheibe, for “clear disc”), where there is no overlap of thick and thin filaments. Running through the center of the H zone is a dense line called the M line (from the German Mittelsclzeibe, for “middle disc”). The I bands are also interrupted at the midline by a darker area called the Z disc (from the German Zwischenscheibe, for “between disc”). A sarcomere extends from one Z disc to the successive Z disc. The Z disc serves to anchor the thin filaments to adjacent sarcomeres.

Myofilaments occupy three-dimensional space. The arrangement of the myofilaments at different points in the sarcomere is shown in Figure 2-5, D and F. Notice that in regions where the thick and thin filaments overlap, each thick filament is surrounded by six thin filaments and each thin filament is surrounded by three thick filaments.

A sarcomere consists of more than just contractile and regulatory proteins. Proteins of the cytoskeleton provide much of the internal structure of the muscle cell. Figure 2-6 diagrams the cytoskeleton of the sarcomere and its relationship to the contractile proteins.⁶ The M line and the Z disc hold the thick and the thin filaments in place, respectively. The elastic filament helps keep the thick filament in the middle between the two Z discs during contraction.

Figure 2-6 Representation of auxiliary proteins in the sarcomere.

(From Billeter R, Hoppeler H: Muscular basis of strength. In Komi PV, editor: Strength and power in sport, p. 45, Champaign, Ill, 1992, Human Kinetics.)

Thick Filaments

Thick filaments are composed primarily of myosin molecules (Figure 2-7). Each molecule of myosin has a rodlike tail and two globular heads (Figure 2-7, A). A typical thick filament contains approximately 200 myosin molecules.⁴ These molecules are oriented so that the tails form the central rodlike structure of the filament (Figure 2-7, B). The globular myosin heads extend outward and form cross-bridges when they interact with thin filaments. The myosin heads have two reactive sites: One allows it to bind with the actin filament, and one binds to ATP. Only when the myosin heads bind to the active sites on actin, forming a cross-bridge, does contraction occur.

Figure 2-7 Molecular organization of thick filaments. A, Individual myosin molecules have a rodlike tail and two globular heads. B, Individual molecules are arranged so that the tails form a rodlike structure and the globular heads project outward to form cross-bridges. C, Myosin subunits are oriented in opposite directions along the filament, forming a central bare zone in the middle of the filament (H zone). D, Thick filament (myosin) within a single sarcomere showing the myosin heads extending toward the thin filament.

(From Plowman SA, Smith DL: Exercise physiology for health, fitness, and performance, ed 2, San Francisco, 2003, Benjamin Cummings.)

The myosin subunits are oriented in opposite directions along the filament, forming a central section that lacks projecting heads (Figure 2-7, C). The result is a bare zone in the middle of the filament, which accounts for the H zone seen in the middle of the A band (Figure 2-7, D).

Thin Filaments

Thin filaments are composed primarily of the contractile protein actin. As illustrated in Figures 2-8, A and B, actin is composed of small globular subunits (G actin) that form long strands called fibrous actin (F actin). A filament of actin is formed by two strands of F actin coiled about each other to form a double helical structure; it resembles two strands of pearls wound around each other and may be referred to as a coiled coil (Figure 2-8, C). The actin molecules contain active sites to which myosin heads will bind during contraction.

Figure 2-8 Molecular organization of thin filaments. A, Individual actin subunits (globular, G actin) shown with active site for binding to myosin heads. B, Fibrous actin (F actin). C, Actin filament with two strands of fibrous actin wound around itself to form a coiled coil. Active sites are exposed. D, Tropomyosin is a regulatory protein that covers the binding sites on actin. E, Troponin is a regulatory protein that, when bound to Ca²⁺⁺, removes tropomyosin from its blocking position on actin. F, The thin filament is composed of actin, tropomyosin, and troponin.

(From Plowman SA, Smith DL: Exercise physiology for health, fitness, and performance, ed 2, San Francisco, 2003, Benjamin Cummings.)

The thin filaments also contain the regulatory proteins called tropomyosin and troponin, which regulate the interaction of actin and myosin. Tropomyosin is a long, double-stranded, helical protein that is wrapped about the long axis of the actin backbone (Figure 2-8, D). Tropomyosin serves to block the active site on actin, thereby inhibiting actin and myosin from binding under resting conditions.

Troponin is a small, globular protein complex composed of three subunits that control the position of the tropomyosin (Figure 2-9). The three units of troponin are troponin C (Tn-C), troponin I (Tn-I), and troponin T (Tn-T). Tn-C contains the calcium-binding sites, Tn-T binds troponin to tropomyosin, and Tn-I inhibits the binding of actin and myosin in the resting state (Figure 2-9, B). When calcium binds to the Tn-C subunit, the troponin complex undergoes a configurational change. Because troponin is attached to tropomyosin, the change in the shape of troponin causes tropomyosin to be removed from its blocking position, thus exposing the active sites on actin.^3,4 Once the active sites are exposed, the myosin heads can bind to the actin, forming the cross-bridges (Figure 2-9, C). Thus calcium is the key to controlling the interaction of the filaments and therefore muscle contraction.

Figure 2-9 Regulatory function of troponin and tropomyosin. A, Troponin is a small globular protein with three subunits. B, Resting condition: Tropomyosin blocks the active sites on actin, preventing actin and myosin from binding. C, Contraction: When troponin binds with Ca²⁺, it undergoes a configurational change and pulls tropomyosin from the blocking position on the actin filament, following myosin heads to form cross-bridges with actin.

(From Plowman SA, Smith DL: Exercise physiology for health, fitness, and performance, ed 2, San Francisco, 2003, Benjamin Cummings.)

The Sliding-Filament Theory of Muscle Contraction

A great deal of data has been amassed since the 1950s on the basis of x-ray, light microscopic, and electron microscopic studies to support the sliding-filament theory of muscle contraction. The basic principles of this theory are summarized in three statements:

Excitation-Contraction Coupling

Excitation-contraction coupling refers to the sequence of events by which an AP (an electrical event) in the sarcolemma of the muscle cell initiates the sliding of the myofilaments, resulting in contraction (a mechanical event). Excitationcontraction coupling can be categorized into three phases:

Figure 2-10 summarizes the events that occur during each phase of excitation-contraction coupling. Excitation-contraction coupling begins with depolarization and spread of an AP along the sarcolemma (point 2 in Figure 2-10) and continues with the propagation of the AP into the T tubules (point 2 in Figure 2-10). An AP in the T tubules causes the release of calcium from the lateral sacs of the sarcoplasmic reticulum (point 3 in Figure 2-10).

Figure 2-10 Phases of excitation-contraction coupling.

(From Plowman SA, Smith DL: Exercise physiology for health, fitness, and performance, ed 2, San Francisco, 2003, Benjamin Cummings.)

When calcium is released from the sarcoplasmic reticulum (the second phase), it binds to the troponin molecules on the thin filament. The binding of calcium to troponin causes troponin to undergo a configurational change, thereby removing tropomyosin from its blocking position on the actin filament (point 4 in Figure 2-10). The third phase of excitation-contraction coupling is the cross-bridging cycle (point 5 in Figure 2-10). The cross-bridging cycle describes the cyclic events that are necessary for the generation of force or tension within the myosin heads during muscle contraction. The generation of tension within the contractile elements results from the binding of the myosin heads to actin and the subsequent release of stored energy in the myosin heads. As shown in Figure 2-11, four individual steps are necessary for the cross-bridging cycle^3,4,7:

Figure 2-11 Force generation of the contractile elements: the cross-bridging cycle.

(From Plowman SA, Smith DL: Exercise physiology for health, fitness, and performance, ed 2, San Francisco, 2003, Benjamin Cummings.)

The first step in the cross-bridge cycle is the binding of activated myosin heads (^*M) with the active sites on actin, forming cross-bridges. In Figure 2-11 a centered dot (·) is used to indicate binding, and an asterisk (^*) is used to indicate activated myosin heads. Thus A·^*M indicates that the activated myosin heads are bound to actin (A), whereas A + M indicates that actin and myosin are unbound.

The second step in the cross-bridging cycle is the power stroke. During this step, activated myosin heads swivel from their high-energy, activated position to a low-energy configuration (M with no ^*). This movement of the myosin cross-bridges results in a slight displacement (sliding) of the thin filament over the thick filament toward the center of the sarcomere. As shown in Figure 2-11, during the second step ADP and P_i are released from the myosin heads, resulting in myosin bound only to actin (A·M).

The third step involves the binding of ATP to the myosin heads and subsequent dissociation (detachment) of the myosin cross-bridges from actin, which produces A + M·ATP. The binding of ATP molecules to the myosin heads allow the myosin heads to detach from actin. In the fourth step the breakdown of ATP provides the energy to activate the myosin heads (^*M). Activation of the myosin heads is extremely important because it provides the cross-bridges with stored energy to move the actin during the power stroke. The breakdown of ATP at this step depends on the presence of myosin ATPase (also known as myofibrillar ATPase), as depicted in the following reaction:

Notice that the products of ATP hydrolysis, ADP + P_i, remain bound to the myosin heads and that the myosin is now in its high-energy or activated state.

The cross-bridging cycle continues as long as ATP is available and calcium is bound to troponin (Tn-C), causing the active sites on actin to be exposed. On the other hand, activated myosin remains in the resting state awaiting the next stimulus if calcium is not available in sufficient concentration to remove tropomyosin from its blocking position on actin (see step 4b in Figure 2-11). Because each cycle of the myosin cross-bridges barely displaces the actin, the myosin heads must bind to the actin and be displaced many times for a single contraction to occur. Thus myosin makes and breaks its bond with actin hundreds or even thousands of times during a single muscle twitch. In order for this make-and-break cycle to occur, myosin heads must detach from actin and then be reactivated. This detaching and reactivating process requires the cycle to be repeated and requires the presence of ATP (see step 3).⁴ The analogy of a spring-loaded mousetrap may be helpful for understanding the role of ATP in providing energy to activate the myosin head. It takes energy to set the trap, just as it takes the splitting of ATP to set or activate the myosin head. Once set, however, the trap releases energy when it is sprung. In a similar manner, the myosin head possesses stored energy, which is released when the myosin heads bind to actin and swivel.

A review of Figure 2-11 reveals that ATP plays several important roles in muscle contraction.