Perchlorate potentiation of excitation-contraction coupling in mammalian skeletal muscles
Gallant, E.M.; Taus, N.S.; Fletcher, T.F.; Lentz, L.R.; Louis, C.F.; Mickelson, J.R.
American Journal of Physiology 264(3 Pt 1): C559-C567
1993
ISSN/ISBN: 0002-9513 PMID: 8384784 Document Number: 422045
The action of perchlorate (ClO-4-), 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 ClO-4- on mechanical parameters was investigated in isolated murine limb muscles. The presence of ClO-4- (5 or 10 mM) greatly increased twitch tension ( gt 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 ClO-4-. However, in whole cell patch-clamp studies of mouse myotubes, contractile activation was shifted by approximately -10 mV by 10 mM ClO-4-. To further define the site of alteration of EC coupling by ClO-4-, 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 ClO-4-. However, neither the affinity nor level of (3H)PN200-110 binding to TT vesicles was significantly affected by ClO-4- 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 ClO-4-, and the current-voltage relationship was shifted approximately -7mV. Thus, in enhancing EC coupling in mammalian muscle, ClO-4- may act at multiple sites including the SR Ca release channel and the TT Ca channel-voltage sensor.