G-protein mediating the slow depolarization induced by FMRFamide in the ganglion cells of Aplysia

Abstract Application of FMRFamide (Phe-Met-Arg-Phe-NH 2 ) induced a slow depolarization in neurons of the Aplysia abdominal ganglion. In voltage-clamped cells, FMRFamide induced a slow inward current that increased when the membrane was depolarized beyond −85 mV, showing a negative slope conductance. However, this inward current never reversed to outward current when hyperpolarized beyond the equilibrium potential for K + . The FMRFamide-induced response was markedly augmented in Ca 2+ -free media, but depressed in Na + -free media. It was unaffected by a change in external potassium. Intracellular injection of guanosine 5′- O -(2-thiodiphosphate) (GDPβS) significantly depressed the FMRFamide response in a dose-dependent way. Injection of cholera toxin (CTX) which did not cause any current response, selectively and irreversibly blocked the FMRFamide response. Neither 3′-deoxyadenosine, an inhibitor of adenylate cyclase, nor H-8, an inhibitor of cyclic adenosine 3′,5′-monophosphate (cyclic AMP)-dependent kinase, depressed the FMRFamide response. 3-Isobutyl-1-methylxanthine (IBMX) did not augment the FMRFamide response appreciably. The FMRFamide response was not occluded at all by a relatively large injection of 8-bromo-cyclic AMP. It was concluded that the FMRFamide response is produced by the opening of the voltage-dependent Na + -channels via activation of a certain CTX-sensitive G-protein which is different from conventional “Gs” that activates adenylate cyclase.