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 (Q1), (2) the charge movement measured in fibres inactivated by depolarization (Q2) and (3) on the steady state VDI of Q1 and Ca2+ release. Our findings were: (1) The central voltage of Q1 was negatively displaced by perchlorate from −29.0 ± 1.6 to −38.4 ± 1.7 mV (n = 4). The maximum Q1 was not significantly affected while the slope of the Q1 vs. V was increased by perchlorate. (2) The central voltage of Q2 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 Q1 went from −39.3 ± 1.8 to −48.6 ± 1.2 mV (mean ± SEM, n = 6). Perchlorate had a paradoxical effect on Ca2+ 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 μM/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 μM/ms, n = 9). The above findings suggest that the effect on the steady state inactivation is a direct consequence of the negative shift in Q1 activation. The negative shift in the steady state inactivation of Q1 correlated well with the effect on Ca2+ release.