A model of crossbridge action: the effects of ATP, ADP and Pi.
We have explored a model of crossbridge kinetics that explains many of the effects on steady-state muscle contraction of ligands that bind to the nucleotide site on myosin. The mathematical model follows the basic framework for crossbridge function first established by A. F. Huxley. In the model, detached crossbridges initially bind in a weakly attached, A.M.D.Pi state (A, actin; M, myosin; D, ADP; Pi, orthophosphate) at the beginning of the region of positive force production. Pi release then results in transition to a strongly-bound A.M.D state, as has been suggested by other investigators from both biochemical and mechanical data. Mg2+ ADP release and subsequent crossbridge detachment due to Mg2+ ATP binding to the A.M state occur at the end of the region of positive force production. Work in a number of laboratories has now defined the effects on steady-state contraction of variations in the concentrations of Mg2+ ATP, Mg2+ ADP and Pi. These data provide valuable constraints that can be used to further refine current models. The maximum velocity of shortening (V max) and ATPase activity of muscle fibres exhibit classical saturation behaviour with respect to Mg2+ ATP concentration, with Mg2+ ADP acting as a competitive inhibitor. The model can reproduce this behaviour. The model also explains the observations that increasing [Mg2+ ATP] decreases isometric tension and increasing [Mg2+ ADP] increases tension. As the concentration of Pi increases, model predictions suggest that tension should decrease approximately as log[Pi], that ATPase activity should decrease less than tension and that V max should be almost unchanged, as has been found experimentally. The model also demonstrates that the connection between the parameters of contraction and the free energy of hydrolysis of Mg2+ ATP can be complex.
Pate
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Department of Mathematics, Washington State University, Pullman 99164.
Cooke
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R
D000205:Actomyosin / Q000502:physiology*; D000244:Adenosine Diphosphate / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D007700:Kinetics; D008954:Models, Biological; D009119:Muscle Contraction; D009132:Muscles / Q000502:physiology*; D009218:Myosins / Q000502:physiology; D010710:Phosphates / Q000502:physiology*; D013816:Thermodynamics
D010710:Phosphates; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000205:Actomyosin; D009218:Myosins