The peptide FMRFa terminates a discharge in Aplysia bag cell neurons by modulating calcium, potassium, and chloride conductances.

1. Electrical stimulation of an afferent nerve triggers a 30-min period of firing of action potentials in the bag cell neurons of Aplysia californica. This afterdischarge causes the animal to undergo a long-lasting sequence of stereotyped reproductive behaviors culminating in laying of eggs. The connective sheath surrounding the clusters of bag cell neurons is interspersed with a network of particles that are immunoreactive to an antiserum raised against the tetrapeptide neurotransmitter Phe-Met-Arg-Phe-amide (FMRFa). Because the sheath is known to be rich in processes from the bag cell neurons, these data suggest that an FMRFa-like peptide may be located in neuronal processes that are in close contact with those of the bag cell neurons. 2. Application of FMRFa to bag cell neurons in intact abdominal ganglia effectively suppresses the onset of the afterdischarge in response to electrical stimulation and terminates an ongoing afterdischarge in a reversible manner. 3. Application of FMRFa to isolated bag cell neurons in primary cell culture causes an attenuation of the amplitude of evoked action potentials. This could be attributed in part to an attenuation of the voltage-activated calcium current, which in voltage-clamp experiments was found to be reduced by 10-40%. 4. Application of FMRFa to bag cell neuron in primary culture also causes a hyperpolarization of the membrane potential by activating an outward current with a reversal potential of approximately -67 mV. Ion substitution experiments, together with application of channel blockers, indicate that this current is carried by both potassium and chloride ions. Activation of this current is suppressed by treatment of the cells with either a cyclic AMP analogue or a phorbol ester activator of protein kinase C. 5. FMRFa exerts a powerful inhibitory influence on the bag cell neurons by altering the properties of ion currents involved in both the generation of action potentials and control of the resting potential. This suggests that this neuropeptide plays a role in the regulation of the onset of afterdischarge in vivo.