The "steric blocking model," the "six-state model," and the ATPase activity of regulated actomyosin.

There has been a great deal of interest in the regulation of muscle contraction. Prior biochemical studies have demonstrated that the binding of regulated actin to S-1-ATP is unchanged at low Ca2+, even though the ATPase activity of regulated actomyosin is inhibited under these conditions. Prior structural studies using X-ray diffraction techniques have suggested that the tropomyosin-troponin complex may move and inhibit the actomyosin interaction at low Ca2+ (i.e., steric blocking). In physiologic fiber experiments, "weak" binding crossbridges have been found to bind to the actin filament at low Ca2+, especially at low ionic strength, and other experiments have suggested that Pi release is not directly regulated by calcium. In biochemical studies in the absence of ATP, inhibition of the binding of strong binding states have been reported in both equilibrium and transient kinetic studies. The current work suggests that all of these observations can be explained in terms of a six-state model in which regulation affects one particular actomyosin state that contains both strongly bound ADP and Pi. This further implies that regulation affects both a kinetic transition as well as a weak binding constant.