Thursday, March 15, 2012

Mechanisms of Muscle Contraction

The term contraction, as used in muscle physiology, does not necessarily mean "shortening". It simply refers to activation of the force-generating sites within muscle fibers: the cross-bridges. For example, holding a dumbbell at a constant position requires muscle contraction but not muscle shortening. Following contraction, the mechanisms that initiate force generation are turned off, and tension declines, allowing relaxation of the muscle fiber. When force generation produces shortening of a skeletal muscle fiber, the overlapping thick and thin filaments in each sarcomere move past each other, propelled by movements of the cross-bridges. During this shortening of the sarcomeres, there is no change in the lengths of either the thick or thin filaments. This is known as the sliding-filament mechanism of muscle contraction.

During shortening, each myosin cross-bridge attached to a thin filament actin molecule moves in an arc much like an oar on a boat. This swiveling motion of many cross-bridges forces the thin filaments attached to successive Z lines toward the center of the sarcomere, thereby shortening the sarcomere. One stroke of a cross-bridge produces only a very small movement of a thin filament relative to a thick filament. As long as a muscle fiber remains activated, however, each cross-bridge repeats its swiveling motion many times, resulting in large displacements of the filaments. Thus, the ability of a muscle fiber to generate force and movement depends on the interaction of the contractile proteins actin and myosin.

An actin molecule is a globular protein composed of a single polypeptide that polymerizes with other actins to form two intertwined helical chains. These chains make up the core of a thin filament. Each actin molecule contains a binding site for myosin. The myosin molecule, on the other hand, is composed of two large polypeptide heavy chains and four smaller light chains. These polypeptides combine to form a molecule that consists of two globular heads (containing heavy and light chains) and a longtail formed by the two intertwined heavy chains. The tail of each myosin molecule lies along the axis of the thick filament, and the two globular heads extend out to the sides, forming the crossbridges. Each globular head contains two binding sites, one for actin and one for ATP. The ATP binding site also serves as an enzyme—an ATPase that hydrolyzes the bound ATP.

The myosin molecules in the two ends of each thick filament are oriented in opposite directions, such that their tail ends are directed toward the center of the filament. Because of this arrangement, the power strokes of the cross-bridges move the attached thin filaments at the two ends of the sarcomere toward the center during shortening. The sequence of events that occurs between the time a cross-bridge binds to a thin filament, moves, and then is set to repeat the process is known as a cross-bridge cycle. Each cycle consists of four steps: 1) attachment of the cross-bridge to a thin filament; 2) movement of the cross-bridge, producing tension in the thin filament; 3) detachment of the cross-bridge from the thin filament; and 4) energizing the crossbridge so that it can again attach to a thin filament and repeat the cycle. Each cross-bridge undergoes its own cycle of movement independently of the other crossbridges. At any instant during contraction only a portion of the cross-bridges are attached to the thin filaments and producing tension, while others are in a detached portion of their cycle.