title: Actomyosin-ADP states, interhead cooperativity, and the force-velocity relation of skeletal muscle.
abstract: 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.
authors.affiliation: School of Natural Sciences, Linnaeus University, Kalmar, Sweden. alf.mansson@hik.se
authors.forename: Alf
authors.initials: A
authors.lastname: Månsson
mesh_terms: D000205:Actomyosin / Q000737:chemistry*; D000244:Adenosine Diphosphate / Q000737:chemistry*; D000818:Animals; D003198:Computer Simulation; D003599:Cytoskeleton / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D008956:Models, Chemical; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D009218:Myosins / Q000737:chemistry; D013314:Stress, Mechanical; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D000244:Adenosine Diphosphate; D000205:Actomyosin; D009218:Myosins