Cyclic AMP-gated sodium current in neurons of the pedal ganglion of Pleurobranchaea californica is activated by serotonin

L. C. Sudlow and R. Gillette Department of Physiology and Biophysics, University of Illinois, Urbana-Champaign 61801, USA. 1. We studied the roles of adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-gated Na+ current (INa,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. INa,cAMP responses to pulsed injections of cAMP were occluded by 5-HT-induced inward current (I5-HT). Occlusion was qualitatively and quantitatively similar to that observed during steady-state activation of INa,cAMP by tonic iontophoretic injection of cAMP. 2. Those neurons exhibiting occlusion of INa,cAMP during 5-HT application also exhibited depolarization-induced (Ca(2+)-dependent) inactivation of both INa,cAMP and I5-HT. The magnitudes of the inactivation to depolarizing pulses of I5-HT or INa,cAMP were similar. Recoveries from inactivation for I5-HT and INa,cAMP followed similar exponentially decaying time courses. 3. The decay rate of the INa,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 INa,cAMP was increased by larger tonic cAMP injections, the decay rate of super-imposed INa,cAMP responses to pulsed injections of cAMP was slowed as would be expected from saturation of endogenous phosphodiesterase activity. The decay of INa,cAMP responses to pulsed cAMP injections superimposed on I5-HT were similarly slowed, suggesting that 5-HT action is mediated specifically by cAMP. 4. The decay rate constants for INa,cAMP responses to pulsed injections of cAMP superimposed on I5-HT did not differ from those of INa,cAMP responses superimposed on equivalent, background steady-state INa,cAMP induced by tonic injection of cAMP.