AJP - Cell Physiology, Vol 264, Issue 3 C559-C567, Copyright © 1993 by American Physiological Society

ARTICLES

Perchlorate potentiation of excitation-contraction coupling in mammalian skeletal muscles

E. M. Gallant, N. S. Taus, T. F. Fletcher, L. R. Lentz, C. F. Louis and J. R. Mickelson
Graduate Program in Veterinary Biology, University of Minnesota, St. Paul 55108.

The action of perchlorate (ClO4-), an agonist of the voltage sensor in excitation-contraction (EC) coupling, has been examined using bundles of intact muscle cells, isolated membrane vesicles [sarcoplasmic reticulum (SR) and transverse tubule (TT)], and cultured myotubes. The effect of ClO4- on mechanical parameters was investigated in isolated murine limb muscles. The presence of ClO4- (5 or 10 mM) greatly increased twitch tension ( > 250%), slightly enhanced tetanic tension, and increased K contracture tension. K contracture thresholds of extensor digitorum longus (EDL, 40 mM K+) and soleus (30 mM K+) muscles were not altered by ClO4-. However, in whole cell patch clamp studies of mouse myotubes, contractile activation was shifted by approximately -10 mV by 10 mM ClO4-. To further define the site of alteration of EC coupling by ClO4-, studies were conducted with isolated porcine SR and TT vesicles and with cultured mouse myotubes. The rate constant of Ca-induced 45Ca release from SR vesicles was significantly increased by ClO4-. However, neither the affinity nor level of [3H]PN200-110 binding to TT vesicles was significantly affected by ClO4- concentrations that increased twitch tension. Furthermore, slow plasmalemmal Ca currents of myotubes recorded in the whole cell patch-clamp mode were enhanced by 10 mM ClO4-, and the current-voltage relationship was shifted approximately -7mV. Thus, in enhancing EC coupling in mammalian muscle, ClO4- may act at multiple sites including the SR Ca release channel and the TT Ca channel-voltage sensor.

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