Skeletal muscle cells, commonly called muscle fibers, are multinucleated syncytia formed during development by fusion of mononucleated precursor cells, the myoblasts. They measure 10–100 μm in diameter and can have lengths from a few millimeters up to almost a meter. The hundreds of nuclei are located in the cells’ periphery close to the plasma membrane, whereas most of the cytoplasm is occupied by the longitudinally arrayed myofibrils composed of the myofilaments: thick filaments assembled from myosin II molecules containing rod-shaped segments and globular heads projecting out of the filaments, and thin filaments composed of actin. The contractile myofilaments myosin and actin are organized by specialized proteins of the “sarcomeric cytoskeleton,” which include alpha-actinin and myomesin, as well as the giant proteins nebulin, obscurin, and titin. They fulfill structural and mechanical functions and have roles in signaling. The electron micrograph shows part of the cytoplasm of a striated muscle fiber with parallel arrays of myofibrils. Mitochondria are lined in the small cytoplasmic cords between the myofibrils, where glycogen is accumulated. Profiles of the sarcoplasmic reticulum forming triads (arrows; cf. also Fig. 170) are visible.

The cross-banded pattern apparent in the cytoplasm of the muscle fiber reflects the arrangement, in register, of the myofibrils, and the banded pattern of the myofibrils reflects the arrangement of the myofilaments. Intensely stained A-bands (A – anisotropic), for which the myosin filaments account, and less intensely stained I-bands (I – isotropic), composed mainly of actin filaments, can be discriminated. The dense Z-lines in the center of the I-bands represent sections of disk-shaped platforms, where the actin filaments are anchored by alpha-actinin. Nebulin wraps around the actin filaments and assists alpha-actinin in anchoring the actin filaments. Further accessory proteins are tropomodulin, an actin-capping protein, which regulates the length of the actin filaments, and titin, a giant elastic molecule that connects the thick myosin filaments with the Z-disk. In the center of each A-band, a less dense band, the H-band, corresponds to the central part of the myosin filaments being bare of myosin head projections. The H-band is bisected by a narrow dense line, the M-line built by myosin-binding proteins that hold the thick filaments in register. An intermediate filament lattice of desmin forms stabilizing cross-links between neighboring myofibrils, which are connected with the plasma membrane and extracellular matrix via costameres, juxtaposed to the Z- and M-lines. Dystrophin, a rod-shaped, dimeric protein localized beneath the plasma membrane, links the cytoskeleton of the muscle fiber to the extracellular matrix by binding actin and a complex of transmembrane proteins, the dystroglycans and sarcoglycans, which are connected with laminin and agrin in the basal lamina.

A myofibril segment delineated by two adjacent Z-lines is defined as a sarcomere, the basic contractile unit of the striated muscle shown in the inset. Excluding the H-band, actin and myosin filaments interdigitate. Rapid contraction cycles of well-defined subsequent stages involving attachment, release, bending, force generation, and reattachment of myosin heads to actin molecules move the thin actin filaments along the thick myosin filaments, leading to a shortening of the sarcomeres and contraction of the muscle. Tropomyosin and three troponin molecules have pivotal roles in the initiation of contraction triggered by binding of Ca²⁺ to one of the troponins. This leads to an uncovering of the myosin binding sites located at the actin molecules. Contraction of adjacent sarcomeres occurs with a short time delay.

For muscle contraction, Ca²⁺ must be available as it is required for the binding between myosin and actin, and after contraction, Ca²⁺ must be removed. The rapid delivery and removal of Ca²⁺ is effected by a complex membrane system that surrounds each myofibril and consists of two parts: a longitudinally oriented part, the longitudinal or L-system, a muscle cell-specific endoplasmic reticulum, called sarcoplasmic reticulum, which forms networks of cisternae around the myofibrils and is the major intracellular calcium store, and a transversely oriented part, the transverse tubule or T-system representing tubular projections of the plasma membrane that encircle each myofibril. At particular sites, the two parts of the membrane system come together forming specialized signal transduction organelles, the triads. Triads consist of two terminal cisterns of the L-system associated with a central T-tubule segment. The main function of the triads is to translate the action potential from the plasma membrane to the sarcoplasmic reticulum, effecting calcium flow into the cytoplasm and the initiation of muscle contraction.

In both panels A and B, triads are visible. In panel A, indicated by arrows, triads are apparent in cytoplasmic cords between superficially localized myofibrils. At each side, the central T-tubule is accompanied by a globular profile of a terminal cistern of the L-system. Flatly sectioned triads are visible in panel B. It is evident that terminal cisterns of the L-system are associated with segments of T-tubules at particular sites. The intermembraneous narrow cytoplasmic slits between the T-tubule and L-cistern membranes contain dense materials visible as a fine line, which may correspond to parts of the protein complexes involved in signal transmission. Voltage sensor proteins in the T-tubule membrane of the triads are activated when the plasma membrane depolarizes, leading to conformational changes of the proteins that, in turn, opens gated Ca²⁺-release channels in the membrane of the adjacent terminal cisterns of the L-system effecting rapid release of Ca²⁺ into the cytoplasm. Simultaneously, Ca²⁺ is transported back into the terminal cisterns by Ca²⁺-activated ATPases in the L-system membrane. In the skeletal muscle fibers, triads are regularly localized at the A-I-band junctions.