ISOPROTERENOL AND GTP-GAMMA-S INHIBIT L-TYPE CALCIUM CHANNELS OF DIFFERENTIATING RAT SKELETAL-MUSCLE CELLS

In adult skeletal muscle, G-proteins have been shown to modulate the c alcium channels both directly and through a cAMP-dependent phosphoryla ting mechanism. We have investigated the action of G-proteins on the L -type calcium current in cultured rat muscle cells (myoballs) under vo ltage clamp in whole cell or perforated patch modes. Intracellular pho tolytic release of 200 mum GTP(gamma)S inhibited the L-type calcium cu rrent. Inclusion of 500 muM uncaged GTP(gamma)S in the patch pipette i n the whole cell configuration reduced the calcium current by a simila r amount. Under perforated patch conditions external application of 10 muM of the beta-adrenergic agonist isoproterenol also reduced the cal cium current. Pretreatment of the cells with pertussis toxin reversed the effect of GTP(gamma)S and removed that of isoproterenol. We conclu de that rat myoballs contain beta-adrenergic receptors that inhibit th e L-type calcium current, and that this inhibition is mediated by a pe rtussis toxin-sensitive protein.