A model of the release of myosin heads from actin in rapidly contracting muscle fibers.
We describe a model that relates the maximum shortening velocity of a muscle fiber, Vm, to the kinetics of the dissociation of a myosin head from actin. At Vm, the positive work exerted by cross-bridges attached in the powerstroke must be balanced by cross-bridges that have been carried by movement of the filaments into a region where they exert a negative force. This balance allows one to relate Vm and the rate of cross-bridge detachment. Studies of actomyosin kinetics suggest that at high substrate, detachment should be limited by a slow protein isomerization (approximately 50 s-1) that precedes ADP release. This rate is too slow to be easily accommodated in existing models. However, a slow rate for cross-bridge dissociation, similar to that of the isomerization, is predicted if previous models are modified to include rapid detachment of cross-bridges that have been carried so far into the negative force region that their free energy exceeds that of the detached state. The model also explains another aspect of muscle contraction: at high shortening velocities, the observed rate of ATP hydrolysis is low, because a cross-bridge can interact with multiple actin binding sites before releasing the hydrolysis products and binding another ATP.
Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
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Cooke
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White
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Pate
D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D055592:Biophysical Phenomena; D001703:Biophysics; D003198:Computer Simulation; D004734:Energy Metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D009218:Myosins / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
D000199:Actins; D000255:Adenosine Triphosphate; D009218:Myosins