A weakly coupled version of the Huxley crossbridge model can simulate energetics of amphibian and mammalian skeletal muscle

This study aimed to establish whether quantitatively accurate predictions o f the rate of crossbridge-dependent energy output from shortening muscle co uld be made on the basis of a 2-state model of crossbridge kinetics incorpo rating weak coupling between mechanical cycles and ATP hydrolysis. The mode l was based on Huxley's (1957) model but included rapid detachment, without ATP hydrolysis, of crossbridges when their strain energy increased suffici ently that crossbridge free energy exceeded that of the unbound state (Cook e et al., 1994). An expression was derived relating force to steady-state v elocity in terms of the model's rate constants. The values of the rate cons tants that both provided the best fit through force-velocity data and corre ctly predicted crossbridge-dependent rate of energy output during an isomet ric contraction were found and used to predict the variation in rate of ene rgy liberation with shortening velocity. The model predictions closely matc hed the estimated crossbridge energetics of frog sartorius muscle, includin g the decline in rate of enthalpy output at high shortening velocities. Dat a from fast- and slow-twitch muscles of the mouse were also simulated. The velocity-dependence of rate of energy liberation from fast-twitch EDL muscl e was well described by the model. The model overestimated crossbridge-depe ndent energy output from slow-twitch soleus at low shortening velocities bu t provided accurate predictions of energy output at high velocities. In ter ms of this model, the distinctive energetics of fast and slow muscles canno t be explained exclusively by differences in cross-bridge detachment rate; differences in the relative rates of crossbridge attachment must also be co nsidered to explain the different relations between energy output and short ening velocity.