Cyclic AMP modulation of a specific ion channel in an identified nerve cell: possible role for protein phosphorylation.

Multidisciplinary studies of the role of cAMP in synaptic transmission have been made possible by the favorable properties of the molluscan nervous system, and there is now evidence from several laboratories implicating cAMP in physiological responses in various Aplysia nerve and muscle cells (9,10,15,18,21). The results we have obtained satisfy all the criteria (8) necessary to establish that cAMP mediates the response to a neurotransmitter: a) the response is mimicked by intra- or extracellular application of cAMP derivatives, and by activation of adenylate cyclase within R15; b) a phosphodiesterase inhibitor enhances the response to low concentrations of serotonin; c) serotonin causes cAMP to accumulate within R15, and stimulates adenylate cyclase activity in membranes prepared from R15 cell bodies; and d) the serotonin receptors mediating adenylate cyclase stimulation and R15 hyperpolarization are pharmacologically very similar. This is the first time all these criteria have been satisfied in a neuronal system, and thus we conclude that the serotonin-induced increase in potassium conductance in neuron R15 is mediated by cAMP.