title: Simulation of the rapid regeneration of the actin-myosin working stroke with a tight coupling model of muscle contraction.
abstract: A. F. Huxley's suggestion in Nature (1992) that a structural modification in the myosin head driven by phosphate release can explain the rapid regeneration of the working stroke, which follows the quick recovery elicited by a step release of moderate size (3-6 nm per half-sarcomere), has been tested with a theoretical model. It is assumed that, in the shortening muscle, cross-bridges can undergo their work producing interaction in two ways distinct for the biochemical state and for the amount of filament sliding allowed. During shortening at low speed, as well as after a shortening step of moderate size, phosphate release from the cross-bridge in the AM-ADP-P state promotes a 100 s-1 structural change which resets the myosin head in a configuration that allows for a new complete working stroke in the AM-ADP state. In this case the total sliding distance for interaction is about 15 nm. With the increase in shortening velocity a progressively larger fraction of interacting cross-bridges remains in the AM-ADP-P state throughout the working stroke and the sliding distance for interaction is about 11 nm. Reattachment of detached cross-bridges occurs at moderate rate whichever is the pathway from which they originate. The model predicts satisfactorily the time course of the rapid regeneration of the working stroke in double step experiments, but fails to simulate the transition to the steady state response in staircase experiments, the maximum power output during steady shortening and the decrease in rate of energy liberation at high shortening velocities. These results strengthen the conclusion of our previous modelling work where we demonstrated that the condition necessary to fit the mechanical and energetic properties of shortening muscle is to assume two pathways for cross-bridge cycling distinct for the kinetics of detachment and reattachment.
authors: Dipartimento di Scienze Fisiologiche, Firenze, Italy.
authors: G
authors: G
authors: Piazzesi
authors: V
authors: V
authors: Lombardi
mesh_terms: D000199:Actins / Q000502:physiology*; D000818:Animals; D007537:Isometric Contraction; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000502:physiology; D009218:Myosins / Q000502:physiology*; D013997:Time Factors
chemical_list: D000199:Actins; D009218:Myosins