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Sliding Filament Model of Contraction

The length of the thick and thin filaments remains constant during contraction, but the overall sarcomere length becomes shorter. The I band becomes shorter with contraction as the thick filaments slide past the thin filaments in a process known, appropriately, as the sliding filament model of muscle contraction.

The sliding filament model was proposed by both Huxley and Simmons and by Huxley in 1971 and is still the guiding hypothesis for the molecular basis of muscle contraction.

Our current understanding of molecular contraction begins with the hydrolysis of ATP by myosin on the thick filament. This hydrolysis of ATP results in a conformational change of myosin, flexing it approximately 45°.

The myosin binds to the active site on the actin thin filament, forming a cross-bridge. Once cross-bridge formation has occurred, ADP and phosphate are released from the myosin head, facilitating cross-bridge flexion during the myosin molecule conformation, pulling the thin filaments a short distance past the thick filaments. To continue the contraction, myosin must release its bond with the actin molecule. This occurs when another molecule of ATP is bound by the myosin ATPase-binding site.

The ATP molecule is then cleaved, repeating the process numerous times in rapid succession to cause a single contraction. This process produces a ratcheting phenomenon that causes sarcomere shortening.

Sarcomere contraction is regulated by troponin and tropomyosin. Troponin is intimately associated with tropomyosin along the actin thin filament, and it serves as a regulatory protein for contraction.

Troponin has three subunits: I, T, and C. Troponin I is inhibitory and is able to block actin–myosin interaction. Troponin T enables binding of troponin and tropomyosin. Troponin C binds calcium. When myoplasmic calcium concentrations are low, the troponin–tropomyosin complex is situated on the actin filament in a way that prevents actin–myosin cross-bridge formation.

A rise in myoplasmic calcium concentration allows Ca2+ to bind with troponin C. The binding of Ca2+ to troponin causes a conformational change in the troponin I molecule complex that removes the troponin– tropomyosin complex from the actin-binding sites. This change permits myosin–actin cross-bridge cycling.

Even a small increase in the cellular Ca2+ concentration results in a troponin–tropomyosin conformational change. This ensures that many cross-bridges are formed with only small changes in intracellular Ca2+ concentrations.

When Ca2+ concentrations are returned to normal resting levels, troponin I reverts to its inhibitory conformation, and the actin-binding sites are again blocked from forming cross-bridges.

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