Antagonistic Modulation of A K+ Channel Activity by Serotonin and the Peptide FMRFamide in Aplysia Sensory Neurons: Molecular Aspects and Functional Implications

Abstract

Electrophysiological studies have shown that the up- and down-modulation of the activity of a class of K+ channels, named the S-type K+ channels (S channels) in the sensory neurons of Aplysia plays an important role in the regulation of the synaptic trasmission between sensory and motor cells by two functionally antagonistic neuromodulators. Serotonin closes the S channels by cAMP-dependent protein phosphorylation and causes pre-synaptic facilitation, resulting in an increase of transmitter release from the sensory neuron, whereas the peptide FMRFamide increases S channel activity through lipoxygenase metabolites of arachidonic acid and causes pre-synaptic inhibition with decrease of transmitter release from the sensory cell. When both the inhibitory and the facilitatory cascades are activated at the same time, FMRFamide overrides the effect of serotonin on S channel function. Biochemical studies suggest that the peptide can revert or antagonize the increase in protein phosphorylation following serotonin administration by inducing dephosphorylation of a common pool of substrate proteins.