Action of perchlorate on the voltage dependent inactivation of excitation-contraction coupling in frog skeletal muscle fibres.

Perchlorate is an agonist of excitation-contraction coupling (ECC) in skeletal muscle displacing charge movement and release activation towards more negative voltages. Contradictory effects of this compound on the voltage dependent inactivation (VDI) of ECC ranging from no effect to a negative shift have been previously reported. In this study we report the effect of the extracellular application of 8 mM perchlorate to cut frog fibres on: (1) the charge movement that activates release (Q(1)), (2) the charge movement measured in fibres inactivated by depolarization (Q(2)) and (3) on the steady state VDI of Q(1) and Ca(2+) release. Our findings were: (1) The central voltage of Q(1) was negatively displaced by perchlorate from -29.0 +/- 1.6 to -38.4 +/- 1.7 mV (n = 4). The maximum Q(1) was not significantly affected while the slope of the Q(1) vs. V was increased by perchlorate. (2) The central voltage of Q(2) was shifted from -91.6 +/- 1.4 to -102.3 +/- 1.5 mV (n = 4). (3) The central voltage of the steady state inactivation curve of Q(1) went from -39.3 +/- 1.8 to -48.6 +/- 1.2 mV (mean +/- SEM, n = 6). Perchlorate had a paradoxical effect on Ca(2+) release, while potentiated the release flux in fibres held at -90 mV (peak release flux increased from 3.9 +/- 1.1 to 6.8 +/- 1.9 microM/ms, n = 5) it had an inhibitory effect when applied to fibres at a depolarized holding potential (peak release flux decreased from 3.9 +/- 0.9 to 2.0 +/- 0.5 microM/ms, n = 9). The above findings suggest that the effect on the steady state inactivation is a direct consequence of the negative shift in Q(1) activation. The negative shift in the steady state inactivation of Q(1) correlated well with the effect on Ca(2+) release.