sarcomere is filled with long cylindrical filamentous bundles termed myofibrils. Myofibrils have a diameter of 1–2 μm and run parallel to the long axis of the muscle fibers. Myofibrils consist of an end‐to‐end chain‐like arrangement of sarcomeres that contain two types of myofilaments, thick and thin, that lie parallel to the long axis of the myofibril (Figure 3.6). These myofilaments are the contractile proteins of the myofibril. Each thin filament is composed of F‐actin, tropomyosin, and troponin complexes. Troponin is a complex of three subunits: TnT that attaches to tropomyosin, TnC that binds calcium ions, and TnI that inhibits the actin–myosin interaction. Troponin complexes are attached at regular intervals along each tropomyosin molecule. Each thick filament is composed of many myosin heavy‐chain molecules bundled together along their rod‐like tails, with their heads exposed and directed toward neighboring thin filaments. The thick myofilament bundles are held in place by myosin‐binding proteins along the M line (German, Mittelscheiber, middle line). Small globular projections on one end of each heavy chain form the myosin heads that have ATP and actin‐binding sites and the enzymatic capacity to hydrolyze ATP (Figure 3.10). Cross bridges are formed between the thin and thick filaments by the head of the myosin molecules plus a short part of its rod‐like portion. These cross bridges are involved in the conversion of chemical energy to mechanical energy (Brunello et al., 2014). This structural biology generates the force necessary for the contraction of individual muscle fibers, which when bundled together into an entire muscle drive movement of the skeleton (via attachment of muscles and tendons to bones).
Figure 3.6 Structure of a skeletal muscle.
Tortora, G. J., & Derrickson, B. H. (Eds.), (2010). Muscle. In Introduction to the human body, 11th ed., Wiley.
Figure 3.7 A simplified schematic of a sarcomere is shown. A sarcomere is composed of actin and myosin filaments that are organized into a characteristic pattern displaying A‐, I‐, M‐, and Z‐bands.
Modified from Nayak, A. & Amrute‐Nayak, M. (2020). SUMO system – A key regulator in sarcomere organization. FEBS Journal, 287, 2176–2190. https://doi.org/10.1111/febs.15263.
Sarcoplasmic reticulum and calcium storage and release
The sarcoplasmic reticulum of muscles is a membrane‐bound structure that is similar to the smooth endoplasmic reticulum in other cells (a network of membranous tubules in the cytoplasm of eukaryotic cells that is in essence a transportation system). The sarcoplasmic reticulum is a key structure specialized in calcium ion (Ca2+) storage (Figure 3.8). Depolarization of the sarcoplasmic reticulum membrane results in the release of Ca2+ ions. This release is initiated at the specialized neuromuscular junction (to be discussed shortly). For a uniform muscle contraction, the cell membrane of skeletal muscle fibers extends into and penetrates the center of the muscle fiber as a system of transverse (T) tubules that form a complex network encircling the A–I bands of each sarcomere. Adjacent to the opposite sides of each T‐tubule are the expanded terminal cisternae of the sarcoplasmic reticulum. Two small cisternae of the sarcoplasmic reticulum and the T‐tubule form a specialized complex known as a triad. It is this junction where a neurally mediated depolarization of the T‐tubules is transmitted to the sarcoplasmic reticulum, stimulating a quick and widespread release of Ca2+.
It is important to understand that muscle contraction depends on the availability of Ca2+ ions, while muscle relaxation occurs in the absence of Ca2+. The sarcoplasmic reticulum (Figure 3.8) regulates Ca2+ flow necessary for rapid contraction and relaxation cycles. After depolarization of the sarcoplasmic reticulum, Ca2+ ions concentrated within cisterna are passively released into the vicinity of the overlapping thick and thin filaments and bind to troponin. This allows bridging of the actin and myosin molecules. When the membrane depolarization ends, the sarcoplasmic reticulum actively transports the Ca2+ back into the cisternae, ending contractile activity.
Figure 3.8 Diagram of the sarcoplasmic reticulum and T‐tubule system of a mammalian skeletal muscle fiber. The sarcoplasmic reticulum enmeshes fibrils with transverse (T) tubules intersecting them. Invaginations of the T‐tubules occur at the transition point of A and I bands in every sarcomere. The T‐tubules are associated with terminal cisternae of the sarcoplasmic reticulum, forming triads. The cut surface of myofibrils also shows the thin and thick myofilaments. Satellite cells reside along the host muscle fiber, directly above the sarcolemma under the basal lamina of muscle and in proximity to the nuclei of muscle cells. Nerve endings and local capillaries extend along the length of the muscle fiber. The extracellular matrix, not shown here, successively encases each layer.
Mukund, K. & Subramaniam, S. (2019). Skeletal muscle: A review of molecular structure and function, in health and disease. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 12, e1462./John Wiley & Sons/CC BY‐4.0.
Vascularization
Skeletal muscle is highly vascularized and can receive up to 80–85% of the heart’s total cardiac output during heavy exercise (Figure 3.9) (Joyner & Casey, 2015). Muscle contraction requires a great deal of energy and, therefore, large amounts of nutrients and oxygen. Moreover, waste products (e.g., lactic acid) produced during the muscle’s energy production reactions need to be eliminated. For this purpose, large blood vessels and nerves enter the epimysium and divide into branches that spread throughout the muscle in the perimysium and endomysium. Numerous capillaries run longitudinally through the endomysium as an “endomyseal capillary bed.” There are frequent transverse anastomoses between these capillaries, resulting in a fine elongated capillary network that surrounds each muscle fiber.
Function of Skeletal Muscle Components
Proper function of skeletal muscle also requires careful coordination between muscle fibers and their proteins with connective tissues, blood vessels, and nerves. Overall, muscles, using their ability to contract, transmit their forces through tendons onto the endoskeleton (bones and cartilage), which allows the movement of the skeleton.
Figure 3.9 Vascular anatomy within skeletal muscle. (a) Highly organized vasculature with dense capillary networks run parallel to myofibers forming microvascular units optimized for nutrient transfer. Inset: Capillaries are embedded within myofiber sarcolemma, where mitochondria congregate at the contact site between capillary and myofiber.
From: Gilbert‐Honick,
