Modulation of ionic currents in Aplysia motor neuron B15 by serotonin, neuropeptides, and second messengers.

Both 5-HT and the 9 amino acid neuropeptide SCPb modulate 3 ionic currents in B15, enhancing a voltage-dependent inward sodium current, decreasing an outward potassium current and increasing an inward rectifying potassium current. In contrast, FMRFamide decreases a voltage-dependent inward sodium current and increases an outward potassium current. We have also investigated the roles of several second-messenger systems that may be mediating the effects of these modulators. Bath application of membrane permeable analogs of cAMP enhance the voltage-dependent inward sodium current and both 5-HT and SCPb increase cAMP levels in B15, suggesting that cAMP may be mediating part of the observed effects of these transmitters on B15. Experiments with phorbol ester, a protein kinase inhibitor, and a phospholipase inhibitor suggest that the phospholipase C/protein kinase C cascade may decrease an outward potassium current. Thus, 5-HT and SCPb may activate multiple second-messenger systems to modulate 3 ionic currents in B15. Additional studies suggest that a cascade involving arachidonic acid may be involved in mediating part of the FMRFamide responses in B15. These studies are beginning to define molecular mechanisms whereby a neuron differentially modulates multiple ionic currents in response to distinct chemical messengers.