Isoproterenol and GTP gamma S inhibit L-type calcium channels of differentiating rat skeletal muscle cells

Abstract

In adult skeletal muscle, G-proteins have been shown to modulate the calcium channels both directly and through a cAMP-dependent phosphorylating mechanism. We have investigated the action of G-proteins on the L-type calcium current in cultured rat muscle cells (myoballs) under voltage clamp in whole cell or perforated patch modes. Intracellular photolytic release of 200 microM GTP gamma S inhibited the L-type calcium current. Inclusion of 500 microM uncaged GTP gamma S in the patch pipette in the whole cell configuration reduced the calcium current by a similar amount. Under perforated patch conditions external application of 10 microM of the beta-adrenergic agonist isoproterenol also reduced the calcium current. Pretreatment of the cells with pertussis toxin reversed the effect of GTP gamma S and removed that of isoproterenol. We conclude that rat myoballs contain beta-adrenergic receptors that inhibit the L-type calcium current, and that this inhibition is mediated by a pertussis toxin-sensitive G-protein.