pH modulation of the kinetics of a Ca2(+)-sensitive cross-bridge state transition in mammalian single skeletal muscle fibres

Abstract

1. The rate constant of tension redevelopment (ktr) following a rapid release and subsequent re-extension of muscle length has been demonstrated to be Ca2+ sensitive and is thought to reflect the rate-limiting step in the cross-bridge cycle leading to the formation of the strongly bound, force-bearing state. The kinetics of this cross-bridge state transition were investigated at 15 degrees C over a wide range of Ca2+ concentrations while varying pH from 7.00 to 6.20 in rat slow-twitch soleus, rat fast-twitch superficial vastus lateralis (SVL) and rabbit fast-twitch psoas skinned single fibres. 2. At maximal levels of Ca2+ activation, ktr was unaffected by changes in pH from 7.00 to 6.20 while isometric tension was depressed to 0.60 +/- 0.02 P0 (mean +/- S.E.M.) at the low pH in fast-twitch fibres and to 0.78 +/- 0.01 P0 in slow-twitch fibres (P0 is the maximum isometric tension obtained at pH 7.00). 3. At reduced levels of Ca2+ activation, corresponding to pCa (-log [Ca2+]) greater than 5.0, ktr was markedly depressed in all fibre types when pH was lowered. The Ca2+ sensitivity of steady-state isometric tension was also reduced in all fibres at pH 6.20 compared to pH 7.00. 4. The results suggest that pH has a modulatory effect upon an apparent rate constant which is rate limiting in terms of the formation of the strongly bound, force-bearing cross-bridge state. This effect of altered pH may in part account for the reduction in the Ca2+ sensitivity of isometric force at low pH as well as the depression of the rate of rise of tension in living fibres during fatiguing stimulation.