Pertussis toxin prevents presynaptic inhibition by kainate receptors of rat hippocampal [3H]GABA release

Abstract

Kainate receptors are ionotropic receptors, also reported to couple to G_i/G_o proteins, increasing neuronal excitability through disinhibition of neuronal circuits. We directly tested in hippocampal synaptosomes if kainate receptor‐mediated inhibition of GABA release involved a metabotropic action. The kainate analogue, domoate (3 μM), inhibited by 24% [³H]GABA‐evoked release, an effect reduced by 76% in synaptosomes pre‐treated with pertussis toxin. Protein kinase C inhibition attenuated by 82% domoate‐induced inhibition of GABA release whereas protein kinase C activation did not change kainate receptor binding. Thus, domoate inhibition of GABA release recruits G_i/G_o proteins and a protein kinase C pathway.