CYCLIC AMP-GATED SODIUM CURRENT IN NEURONS OF THE PEDAL GANGLION OF PLEUROBRANCHAEA-CALIFORNICA IS ACTIVATED BY SEROTONIN

1. We studied the roles of adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-gated Na+ current (I-Na,I-cAMP) in the serotonin (5-HT)-induced excitation of putatively serotonergic ''G'' neurons of the pedal ganglion of Pleurobranchaea californica. Currents were recorded under voltage clamp during 5-HT application and iontophoretic intracellular cAMP injections. I-Na,I-cAMP responses to pulsed injections of cAMP were occluded by 5-HT-induced inward current (I-5-HT) Occlusion was qualitatively and quantitatively similar to that observed during steady-state activation of I-Na,I-cAMP by tonic iontophoretic injection of cAMP. 2. Those neurons exhibiting occlusion of I-Na,I-cAMP during 5-HT application also exhibited depolarization-induced (Ca2+-dependent) inactivation of both I-Na,I-cAMP and I-5-HT. The magnitudes of the inactivation to depolarizing pulses of I-5-HT or I-Na,I-cAMP were similar. Recoveries from inactivation for I-5-HT and I-Na,I-cAMP followed similar exponentially decaying time courses. 3. The decay rate of the I-Na,I-cAMP response is affected by phosphodiesterase inhibitors and can be taken as a sensitive measure of the rate of cAMP degradation. As background steady-state I-Na,I-cAMP was increased by larger tonic cAMP injections, the decay rate of super-imposed I-Na,I-cAMP responses to pulsed injections of cAMP was slowed as would be expected from saturation of endogenous phosphodiesterase activity. The decay of I-Na,I-cAMP responses to pulsed cAMP injections superimposed on I-5-HT were similarly slowed, suggesting that 5-HT action is mediated specifically by cAMP. 4. The decay rate constants for I-Na,I-cAMP responses to pulsed injections of cAMP superimposed on I-5-HT, did not differ from those of I-Na,I-cAMP responses superimposed on equivalent, background steady-state I-Na,I-cAMP induced by tonic injection of cAMP. Thus 5-HT-induced changes in cAMP degradation rates do not measurably contribute to 5-HT stimulation of endogenous cAMP. 5. These data indicate that the inward current stimulated by 5-HT in the G neurons is largely carried by I-Na,I-cAMP,I- which is stimulated by an increase in endogenous cAMP levels. The increase in cAMP associated with I-5-HT is not accompanied by measurable change in phosphodiesterase activity, and it is likely due in entirety to an increase in the synthetic activity of adenylyl cyclase.