COUPLING CALCIUM-BINDING TO TROPONIN-C AND CROSS-BRIDGE CYCLING IN SKINNED CARDIAC-CELLS

This study examines the coupling of calcium binding to troponin with t he force developed by the cross bridges in the skinned cardiac muscle. It emphasizes the key role of the troponin complex in regulating cros s-bridge cycling and defines four distinct states of the troponin comp lex in the single-overlap region. These include a ''loose-coupling'' s tate, wherein cross bridges can exist in the strong conformation witho ut having calcium hound to the neighbor troponin C. Published simultan eous measurements of the force and the bound calcium are used to calcu late the apparent calcium binding coefficients. The force-length relat ionships at different free calcium concentrations are used to evaluate the cooperative mechanism. The dependence of the affinity of troponin for calcium on the number of force-generating cross bridges is the do minant cooperative mechanism. The proposed loose-coupling model, with a positive feedback of force on calcium binding, describes the role of calcium in force regulation and the force-length relationship in skin ned cardiac muscle. The ability to simulate the rate of force developm ent is demonstrated.