A novel membrane sodium current induced by injection of cyclic nucleotides into gastropod neurones

Injection of cyclic AMP (cAMP) or cyclic GMP into identifiable neurones from several different gastropod species immediately depolarized the cell membranes in a dose-dependent manner. Doses were monitored photometrically and evidence is presented for depolarizing effects following nucleotide injections of as little as 30-35 mumol. The depolarizing effect was reversible and was demonstrated under voltage clamp to be primarily the result of a nucleotide-induced, transient increase in a membrane Na current, INa (cAMP). The charge-carrying species was identified by using ion-substituted salines, reversal potential in low-Na saline, and intracellular ion-sensitive electrode measurements. The current was resistant to tetrodotoxin, ouabain and amiloride. Substituting Trisma, tetramethylammonium or bis-tris propane for Na prevented the induced current, whereas Li substitution did not. Duration of the induced current was greatly prolonged in neurones bathed in the phosphodiesterase inhibitor isobutylmethylxanthine, or following injection of any of several cAMP analogues, indicating that the reversible nature of the current stems primarily from in situ hydrolysis of the injected dose and not current inactivation. Amplitude of the induced current either remained constant or decreased over the voltage range where it could be easily measured, i.e. -30 greater than Vm greater than -100 mV, reflecting a voltage as well as a chemical sensitivity of INa (cAMP).