1. We studied the roles of adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-gated Na+ current (I(Na,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,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,cAMP) by tonic iontophoretic injection of cAMP. 2. Those neurons exhibiting occlusion of I(Na,cAMP) during 5-HT application also exhibited depolarization-induced (Ca2+-dependent) inactivation of both I(Na,cAMP) and I(5-HT). The magnitudes of the inactivation to depolarizing pulses of I(5- HT) or I(Na,cAMP) were similar. Recoveries from inactivation for I(5-HT) and I(Na,cAMP) followed similar exponentially decaying time courses. 3. The decay rate of the I(Na,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,cAMP) was increased by larger tonic cAMP injections, the decay rate of superimposed I(Na,cAMP) responses to pulsed injections of cAMP was slowed as would be expected from saturation of endogenous phosphodiesterase activity. The decay of I(Na,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,cAMP) responses to pulsed injections of cAMP superimposed on I(5-HT) did not differ from those of I(Na,cAMP) responses superimposed on equivalent, background steadystate I(Na,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,cAMP), 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.
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