SKELETAL MUSCLE

Muscle cells or fibers form a long multinucleated syncytium grouped in bundles surrounded by connective tissue sheaths and extending from the site of origin to their insertion (Figure 7-1). The epimysium is a dense connective tissue layer ensheathing the entire muscle. The perimysium derives from the epimysium and surrounds bundles or fascicles of muscle cells. The endomysium is a delicate layer of reticular fibers and extracellular matrix surrounding each muscle cell. Blood vessels and nerves use these connective tissue sheaths to reach the interior of the muscle. An extensive capillary network, flexible to adjust to contraction-relaxation changes, invests individual skeletal muscle cell.

Figure 7-1 General organization of the skeletal muscle

The connective tissue sheaths blend and radiating-muscle fascicles interdigitate at each end of a muscle with regular dense connective tissue of the tendon to form a myotendinous junction. The tendon anchors into a bone through the periosteal Sharpey’s fibers.

Characteristics of the skeletal muscle cell or fiber

Skeletal muscle cells are formed in the embryo by the fusion of myoblasts that produce a postmitotic, multinucleated myotube. The myotube matures into the long muscle cell with a diameter of 10 to 100 μm and a length of up to several centimeters.

The plasma membrane (called the sarcolemma) of the muscle cell is surrounded by a basal lamina and satellite cells (Figure 7-2). We discuss the significance of satellite cells in muscle regeneration. The sarcolemma projects long, finger-like processes—called transverse tubules or T tubules—into the cytoplasm of the cell—the sarcoplasm. T tubules make contact with membranous sacs or channels, the sarcoplasmic reticulum. The sarcoplasmic reticulum contains high concentrations of Ca²⁺. The site of contact of the T tubule with the sarcoplasmic reticulum cisternae is called a triad because it consists of two lateral sacs of the sarcoplasmic reticulum and a central T tubule.

Figure 7-2 Skeletal muscle (striated)

The many nuclei of the muscle fiber are located at the periphery of the cell, just under the sarcolemma.

About 80% of the sarcoplasm is occupied by myofibrils surrounded by mitochondria (called sarcosomes). Myofibrils are composed of two major filaments formed by contractile proteins: thin filaments contain actin, and thick filaments are composed of myosin (see Figure 7-2).

Depending on the type of muscle, mitochondria may be found parallel to the long axis of the myofibrils, or they may wrap around the zone of thick filaments. Thin filaments insert into each side of the Z disk (also called band, or line) and extend from the Z disk into the A band, where they alternate with thick filaments.

The myofibril: A repeat of sarcomere units

The sarcomere is the basic contractile unit of striated muscle (Figure 7-3). Sarcomere repeats are represented by myofibrils in the sarcoplasm of skeletal and cardiac muscle cells.

Figure 7-3 Sarcomere

The arrangement of thick (myosin) and thin (actin) myofilaments of the sarcomere is largely responsible for the banding pattern observed under light and electron microscopy (see Figures 7-2 and 7-3). Actin and myosin interact and generate the contraction force. The Z disk forms a transverse sarcomeric scaffold to ensure the efficient transmission of the generated force.

Thin myofilaments measure 7 nm in width and 1 μm in length and form the I band. Thick filaments measure 15 nm in width and 1.5 μm in length and are found in the A band.

The A band is bisected by a light region called the H band (see Figures 7-3; 7-4). The major component of the H band is the enzyme creatine kinase, which catalyzes the formation of ATP from creatine phosphate and adenosine diphosphate (ADP). We discuss later how creatine phosphate maintains steady levels of ATP during prolonged muscle contraction.

Figure 7-4 Skeletal muscle cell

Running through the midline of the H band is the M line. M-line striations correspond to a series of bridges and filaments linking the bare zone of thick filaments. Thin filaments insert into each side of the Z disk, whose components include α-actinin.

Components of the thin and thick filaments of the sarcomere

F-actin, the thin filament of the sarcomere, is double-stranded and twisted. F-actin is composed of globular monomers (G-actin; see Cytoskeleton in Chapter 1, Epithelium). G-actin monomers bind to each other in a head-to-tail fashion, giving the filament polarity, with barbed (plus) and pointed (minus) ends. The barbed end of actin filaments inserts into the Z disk.

Tropomyosin consists of two nearly identical α-helical polypeptides twisted around each other. Tropomyosin runs in the groove formed by F-actin strands. Each molecule of tropomyosin extends for the length of seven actin monomers and binds the troponin complex (Figure 7-5).

Figure 7-5 Troponin and tropomyosin

Troponin is a complex of three proteins: troponin I, C, and T. Troponin T binds the complex to tropomyosin. Troponin I inhibits the binding of myosin to actin. Troponin C binds Ca²⁺ and is found only in striated muscle.

Myosin II, the major component of the thick filament, has adenosine triphosphatase (ATPase) activity (it hydrolyzes ATP) and binds to F-actin—the major component of the thin filament—in a reversible fashion.

Myosin II consists of two identical heavy chains and two pairs of light chains (Figure 7-6; see Cytoskeleton in Chapter 1, Epithelium). At one end, each heavy chain forms a globular head. Two different light chains are bound to each head: the essential light chain and the regulatory light chain. The globular head has three distinct regions: (1) an actin-binding region; (2) an ATP-binding region; and (3) a light chain–binding region. Myosin II, like the other molecular motors kinesins and dyneins, use the chemical energy of ATP to drive conformational changes that generate motile force. As you recall, kinesins and dyneins move along microtubules. Myosins move along actin filaments to drive muscle contraction.

Figure 7-6 Myosin II

Nebulin (Figure 7-7) is associated with thin (actin) filaments; it inserts into the Z disk and acts as a template for determining the length of actin filaments.

Figure 7-7 Sarcomere: Nebulin and titin

Titin (see Figure 7-7) is a very large protein with a molecular mass in the range of millions. Each molecule associates with thick (myosin) myofilaments and inserts into the Z disk, extending to the bare zone of the myosin filaments, close to the M line. Titin controls the assembly of the myosin myofilament by acting as a template. Titin has a role in sarcomere elasticity by forming a spring-like connection between the end of the thick myofilament and the Z disk.

Z disks are the insertion site of actin filaments of the sarcomere. A component of the Z disk, α-actinin, anchors the barbed end of actin filaments to the Z disk.

Desmin is a 55-kd protein that forms intermediate (10-nm) filaments. Desmin filaments encircle the Z disks of myofibrils and are linked to the Z disk and to each other by plectin filaments (Figure 7-8). Desmin filaments extend from the Z disk of one myofibril to the adjacent myofibril, forming a supportive latticework. Desmin filaments also extend from the sarcolemma to the nuclear envelope.

Figure 7-8 Cytoskeletal protective network of a skeletal muscle cell

Desmin inserts into specialized sarcolemma-associated plaques, called costameres. Costameres, acting in concert with the dystrophin-associated protein complex, transduce contractile force from the Z disk to the basal lamina, maintain the structural integrity of the sarcolemma, and stabilize the position of myofibrils in the sarcoplasm.

The heat shock protein αB-crystallin protects desmin filaments from stress-induced damage. Desmin, plectin, and αB-crystallin form a mechanical stress protective network at the Z-disk level. Mutations in these three proteins lead to the destruction of myofibrils after repetitive mechanical stress.

Creatine phosphate: A back up energy source

Creatine phosphate is a back up mechanism to maintain steady levels of ATP during muscle contraction. Consequently, the concentration in muscle of free ATP during prolonged contraction does not change too much.

Figure 7-10 provides a summary of the mechanism of regeneration of creatine phosphate, which takes place in mitochondria and diffuses to the myofibrils, where it replenishes ATP during muscle contraction.