Strong binding of myosin increases shortening velocity of rabbit skinned skeletal muscle fibres at low levels of Ca(2+).

1. At low levels of activation, unloaded shortening of skinned skeletal muscle fibres takes place in two phases: an initial phase of high-velocity shortening followed by a phase of low-velocity shortening. The basis for Ca(2+) dependence of unloaded shortening velocity (V(o)) in the low-velocity phase was investigated by varying the level of thin filament activation with Ca(2+) and N-ethyl-maleimide myosin subfragment-1 (NEM-S1), a non-tension-generating, strong binding derivative of subfragment-1. V(o) was measured with the slack-test method. 2. Treatment of skinned fibres with 5 microM NEM-S1 eliminated the low-velocity phase of shortening but had no effect on the high-velocity phase of shortening during submaximal activation with Ca(2+), or on V(o) during maximal activation with Ca(2+). 3. Extensive washout of NEM-S1 from the treated fibres restored the low-velocity phase of shortening and returned low-velocity V(o) to pre-treatment values. 4. The effect of NEM-S1 to increase low-velocity V(o) can be explained in terms of a model in which strong binding myosin cross-bridges activate the thin filament to a state in which the rate of ADP release from the actin-myosin-ADP complex and the rate of cross-bridge detachment from actin are accelerated during unloaded shortening.