Inhibitory modulation of neuronal voltage-dependent sodium current by Phe-Met-Arg-Phe-amide.

The tetrodotoxin (TTX)-sensitive, voltage-gated Na(+)-current (INa) in a cluster of peptidergic neurons, involved in egg laying, in the CNS of the mollusc Lymnaea stagnalis, is modulated by the neuropeptide FMRFa (Phe-Met-Arg-Phe-NH2). Application of FMRFa reversibly reduced the isolated INa in a dose-dependent fashion. The physiological consequence is that the threshold for action potential generation is increased, causing an arrest of ongoing firing activity. The inhibitory action of FMRFa reported here is the first known example of modulation of the voltage-gated INa by a putative neurotransmitter in intact nerve cells. This finding underlines the importance of modulation of ionic currents as a mechanism of regulation of neuronal excitability and includes the voltage dependent Na current in the range of currents subject to transmitter modulation.