Oxytocin-induced sodium current is mediated by cAMP-dependent protein phosphorylation in an identified snail neuron.

The intracellular biochemical process underlying oxytocin-induced change of membrane properties was analyzed in an identified neuron of Achatina fulica Férussac, using pressure injection technique and pharmacological tools. Oxytocin dose-dependently enhanced the negative slope resistance (NSR) region on the current-voltage relation. The oxytocin-induced current was attenuated by a reduction of extracellular Na+ and not influenced by the addition of 100 microM tetrodotoxin (TTX) to the medium, suggesting that this current is predominantly due to the activation of TTX-resistant Na+ channels. In the Ca2(+)-free state, substituted by an equivalent amount of Co2+, the amplitude of oxytocin-induced current was somewhat reduced at the NSR region but it was not influenced at less than -60 mV. Application of 100 microM isobutylmethylxanthine, a phosphodiesterase inhibitor, augmented the oxytocin-induced current. Pressure injection of 10 mM adenosine 3',5'-cyclic monophosphate (cAMP) elicited a Na(+)-dependent inward current similar to the oxytocin response. The further role of cAMP linked with the oxytocin-induced current was investigated using two kinds of cAMP-dependent protein kinase inhibitors, isoquinolinesulfonamide (H-8) and protein kinase inhibitor (PKI). Extracellular application of H-8 or pressure injection of PKI, prior to oxytocin application, both blocked the oxytocin-induced current. Based on these results, oxytocin-elicited inward currents may mediate cAMP-dependent protein phosphorylation mainly by activation of Na+ channels.