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

Abstract

SUMMARY1. The effect of the perchlorate anion (C104-) on the potential dependence of mechanical and electrical parameters was investigated in skeletal muscle fibres of the frog.2. 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.3. Twitch height was unaffected below 10-4 M-C104-, it usually increased severalfold in the concentration range of 10-3 to 10-2 M-C104 and continued to rise slowly between 10-2 and 10-M-C104-.4. C104-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-C104-). The shift in force activation was not accompanied by a corresponding shift in the potential dependence of force inactivation.5. In the presence of C104-, 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.6. C104-shifted the threshold for the initiation of the action potential only slightly towards more negative potentials (-10 mV at 70 mM-Cl04-). Little or no shift was observed in the lower concentration range (< 10 mM) where the threshold of force activation was shifted by about 20 mV.7. C104-slightly depressed the activation of the delayed rectifier without causing any distinct change in its threshold potential.8. Electrophoretic injection of C104-(internal C104 concentration ([Cl0411) 1 mM) induced similar effects to those following external application of this anion, i.e. a shift of force activation towards more negative potentials.9. Of several other anions tested, only dichromate, which resembles C104 in its tetrahedal structure, similarly caused force activation after repolarization.10. We conclude that at low concentrations (< 10 mM) C104-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.

Intramembrane charge movements in frog skeletal muscle in strongly hypertonic solutions.

“…This complements earlier findings where perchlorate (8-10 mM) facilitated both q~ charge movement and excitation--contraction coupling (Gomolla, Gottschalk, and Luttgau, 1983;Luttgau, Gottschalk, Kovacs, and Fuxreiter, 1983;Huang, 1986Huang, , 1987), yet did not modify calcium current activation (Feldmeyer and Luttgau, 1988). Taken together, these findings make it unlikely that the q~ charge movement reflects a necessary step in calcium current activation, whether by itself or as part of some process that also involves excitation--contraction coupling.…”

The influence of perchlorate ions on complex charging transients in amphibian striated muscle

“…This scheme would require an allosteric coupling mechanism by which RyR-Ca¥ release channels could exert reciprocal actions upon the DHPR-voltage sensors. Nevertheless, it would be compatible with the known chaotropic actions of perchlorate upon interactions between protein complexes in physical contact (Collins & Washabaugh, 1985), provided perchlorate achieves significant concentrations at the relevant intracellular sites (Dilger, McLaughlin, McIntosh & Simon, 1979;Gomolla et al 1983). The likely intricacies of these interactions might then account for the complexities of qã charge movements in systems where they take place.…”

“…Perchlorate both potentiates excitation-contraction coupling (Gomolla et al 1983) and exerts marked effects upon the intramembrane charge movement Perchlorate and allosterically coupled charge Table 6. Interactions between the effects of perchlorate and tetracaine at the level of the qã charge…”

“…The present experiments proceed to examine the actions of perchlorate specifically upon the qã charge in further tests of such a descriptive framework. Earlier studies have demonstrated that perchlorate is a powerful twitch potentiator that also modifies several features of the intramembrane charge even when this was studied as a whole (Gomolla, Gottschalk & Luttgau, 1983;Luttgau, Gottschalk, Kovacs & Fuxreiter, 1983;Huang, 1986Huang, , 1987Gyorke & Palade, 1992). Furthermore, perchlorate may act through the RyR-Ca¥ release channels rather than either the DHPR-voltage sensors or the ionic channels responsible for Ca¥ currents (Feldmeyer & Luttgau, 1988;Gyorke & Palade, 1992;.…”

Calcium signals recorded from cut frog twitch fibers containing antipyrylazo III.

“…For prolonged activation, e.g., during a tetanus, such a rapid rate of removal would require, on the simplest scheme, that many transmitter molecules be produced at each tubular activation site . Since, under certain conditions, nearly maximum activation of contraction can be maintained for as long as 1 min (Gomolla et al ., 1983), the amount of available transmitter or its precursor would need to be large or the stores would need to be replenished rapidly, within seconds.…”