Actomyosin-ADP states, interhead cooperativity, and the force-velocity relation of skeletal muscle.

Despite intense efforts to elucidate the molecular mechanisms that determine the maximum shortening velocity and the shape of the force-velocity relationship in striated muscle, our understanding of these mechanisms remains incomplete. Here, this issue is addressed by means of a four-state cross-bridge model with significant explanatory power for both shortening and lengthening contractions. Exploration of the parameter space of the model suggests that an actomyosin-ADP state (AM( *)ADP) that is separated from the actual ADP release step by a strain-dependent isomerization is important for determining both the maximum shortening velocity and the shape of the force-velocity relationship. The model requires a velocity-dependent, cross-bridge attachment rate to account for certain experimental findings. Of interest, the velocity dependence for shortening contraction is similar to that for population of the AM( *)ADP state (with a velocity-independent attachment rate). This accords with the idea that attached myosin heads in the AM( *)ADP state position the partner heads for rapid attachment to the next site along actin, corresponding to the apparent increase in attachment rate in the model. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.