ADENYLYL-CYCLASE INTEGRATES MULTIPLE G-PROTEIN SIGNALS TO MODULATE CALCIUM CURRENTS IN NEONATAL RABBIT HEART

We investigated the effects of added beta gamma subunits of G proteins (G beta gamma) on beta-adrenergic responsiveness of transmembrane Ca2+ currents (I-Ca) in ventricular myocytes from neonatal rabbits. G beta(1 gamma 1) purified from retinal rods was dialyzed into cells via the voltage clamp micro-electrode. Stimulation of I-Ca by isoproterenol was not affected by added intracellular G beta(1 gamma 1) or by carbachol alone but was completely blocked by combined G beta(1 gamma 1) and carbachol. Pretreatment of cells with pertussis toxin or temporal separation of carbachol and isoproterenol allowed stimulation of I-Ca by isoproterenol in cells dialyzed with G beta(1 gamma 1). Carbachol and G beta(1 gamma)1 together also did not prevent stimulation of I-Ca by dibutyryl-cyclic AMP. Thus, rather than simply inactivating G(s) alpha by mass action, G beta(1 gamma 1) acts in concert with carbachol to inhibit isoproterenol stimulation of I-Ca. (C) 1995 Academic Press, Inc.