Muscle Fiber Anatomy: Biochemical Mechanics of Contraction

Troponin molecules also run the course of the thin filament but occur as complexes bound at regular intervals. Three components comprise troponin: TnI, TnT, and TnC. TnI is an inhibitory molecule that binds actin itself and the other two troponin elements. TnT binds tropomyosin. TnC binds the calcium ion (Ca²⁺), which then leads to a conformational change, ultimately rotating tropomyosin off and unblocking the myosin binding site on actin. Thick filaments are also a polymer but comprising numerous myosin molecules. Myosin is a hexamer of two heavy chains and two pairs of light chains. The heavy chain tails also self-associate to form the backbone of the thick filament. The heads of the heavy chains form the myosin heads, which, after self-assembly, protrude in all directions from the thick filament backbone toward the thin filaments that surround the thick filament in a hexagonal arrangement. One segment of the myosin head binds actin and hydrolyzes adenosine triphosphate (ATP), ultimately leading to a conformational change and “power stroke,” thus flexing the myosin head and sliding the bound actin filament toward the middle of the sarcomere.

The cross-bridge cycle describes the steps by which myosin, actin, ATP, and Ca²⁺ interact to lead to sarcomere shortening and muscle contraction on an elemental level. At rest, ATP is bound to the myosin head and is partially hydrolyzed to adenosine diphosphate (ADP) and phosphate (P_i), the myosin head is “cocked” and available to form a high-affinity bond with actin, but the myosin binding site on actin is obstructed by tropomyosin. After depolarization of the muscle membrane and generation of a muscle fiber action potential, large amounts of Ca²⁺ are released from the sarcoplasmic reticulum. Ca²⁺ binds TnC, causing tropomyosin to “unblock” the myosin binding site on actin. The myosin head then binds actin, forming the “cross-bridge.” ADP and P_i are released from the myosin head. The myosin head flexes on its backbone (the “power stroke”), pulling the bound actin toward the middle of the sarcomere. ATP again binds to the myosin head, which dissociates from actin. ATP is hydrolyzed again to ADP and P_i, the myosin head “recocks,” and the actin binding site on the myosin head is again produced. If Ca²⁺ continues to be available, the sequence of events repeats, and actin is pulled further toward the middle of the sarcomere. When this happens multiple times over multiple “cross-bridges” between multiple myosinactin molecules in multiple thick and thin filaments, the sarcomere shortens. As this occurs along several sarcomeres in the muscle fiber, the muscle fiber shortens. When multiple muscle fibers shorten within a muscle, the muscle contracts. If Ca²⁺ is no longer available, however, myosin binding sites on actin become blocked by tropomyosin, myosin cannot bind actin, and the muscle relaxes.