Perchlorate-induced alterations in electrical and mechanical parameters of frog skeletal muscle fibres

Abstract

The effect of the perchlorate anion (ClO4-) on the potential dependence of mechanical and electrical parameters was investigated in skeletal muscles fibres of the frog. Two main methods were employed: twitches and K contractures were induced in isolated fibres from the semitendinosus or iliofibularis muscle, and point voltage clamp was applied in sartorius and short toe muscle fibres. Twitch height was unaffected below 10(-4) M-ClO4-, it usually increased several-fold in the concentration range of 10(-3) to 10(-2) M-ClO4- and continued to rise slowly between 10(-2) and 10(-1) M-ClO4-. ClO4- caused a parallel shift of the activation curve, which relates peak force to membrane potential, towards more negative potentials by up to 40 mV (70 mM-ClO4-). The shift in force activation was not accompanied by a corresponding shift in the potential dependence of force inactivation. In the presence of ClO4-, maximum force development upon depolarization to -60 or -50 mV could be maintained for several minutes, suggesting that spontaneous relaxation after full depolarization is due to a potential-dependent inactivation process, and not to an exhaustion of Ca2+ release. ClO4- shifted the threshold for the initiation of the action potential only slightly towards more negative potentials (approximately 10 mV at 70 mM-ClO4-). Little or no shift was observed in the lower concentration range (less than 10 mM) where the threshold of force activation was shifted by about 20 mV. ClO4- slightly depressed the activation of the delayed rectifier without causing any distinct change in its threshold potential. Electrophoretic injection of ClO4- (internal ClO4- concentration ([ClO4-]i) approximately 1 mM) induced similar effects to those following external application of this anion, i.e. a shift of force activation towards more negative potentials. Of several other anions tested, only dichromate, which resembles ClO4-in its tetrahedal structure, similarly caused force activation after repolarization. We conclude that at low concentrations (less than 10 mM) ClO4- rather specifically improves excitation-contraction coupling by direct interference with the gating mechanism which activates Ca release from the sarcoplasmic reticulum. At higher concentrations, it may also influence potential-dependent membrane processes by adsorption to the outer surface of the membrane.