During activation, combinations of cycling myosin that contribute insufficient activation energy delay deactivation. We propose that regulatory proteins of the thin filament require the mechanical force of cycling myosin to achieve the transition state for activation. Events that arise during a run and prevent the chance of ending a run for a random interval of time account for the observed run time distributions, suggesting that the events originate with cycling myosin. Further titration with Ca 2+, or adding excess regulatory proteins tropomyosin and troponin, shifted the relative density of short run times to fit the positive slope of a gamma distribution, which derives from waiting times between Poisson events. However, we determined that relative density of observed run times fits an exponential only at low Ca 2+ levels that activate filament gliding. In this scenario, rate is given by the odds of a pause, and hence, run times between pauses fit an exponential distribution that slopes negatively for all observable run times. A classic thermodynamic mechanism predicts that if chemical potential is constant, transitions between runs and pauses of gliding thin filaments will occur at constant rate as given by a Poisson distribution. We tested this hypothesis by measuring time intervals for gliding runs and pauses of individual skeletal muscle thin filaments in cycling myosin motility assays. Vertebrate striated muscle thin filaments are thought to be thermodynamically activated in response to an increase in Ca 2+ concentration.
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