Distinct molecular processes associated with isometric force generation and rapid tension recovery after quick release.

It was proposed by Huxley and Simmons (Nature 1971, 233:533-538) that force-generating cross-bridges are attached to actin in several stable positions. In this concept, isometric force is generated by the same mechanism as the quick tension recovery after an abrupt release of length; i.e., when crossbridges proceed from the first postulated stable position to the second and/or subsequent positions, resulting in straining of the elastic elements within the cross-bridges. Therefore, isometric force is generated by cross-bridges in the second or even subsequent stable positions. However, through mechanical measurements of skinned rabbit psoas muscle fibers, we found that during isometric contraction only the first stable state is significantly occupied; i.e., isometric force is generated by cross-bridges in the first of the stable states. Thus, isometric force and the quick tension recovery appear to result from two distinctly different molecular processes. We propose that isometric force results from a structural change in the actomyosin complex associated with the transition from a weakly bound configuration to a strongly bound configuration before the reaction steps in the Huxley-Simmons model, whereas a major component of quick tension recovery originates from transitions among the subsequent strongly bound states. Mechanical, biochemical, and structural evidence for the two distinct processes is summarized and reviewed.