KAINATE RECEPTOR MODULATION OF GABA RELEASE INVOLVES A METABOTROPIC FUNCTION

The mechanism through which kainate receptors downregulate the release of GABA in the hippocampus is not known. We have found that the actio n of kainate on the hippocampal inhibitory postsynaptic current (IPSC) is mediated by a metabotropic process that is sensitive to Pertussis toxin (PTx) and independent of ion channel current. The downregulation of GABA IPSCs by kainate was also prevented in a dose-dependent manne r by calphostin C, a specific inhibitor of PKC, and the inhibition of phospholipase C (PL.C) drastically reduced the action of kainate. The effect of kainate was completely occluded by phorbol esters and by inc reasing extracellular Ca2+ but remained unaltered after inhibition or activation of protein kinase A (PKA). These results demonstrate that t he activation of kainate receptors triggers a second messenger cascade , which results in the stimulation of PKC, and therefore document a me tabotropic action of kainate receptors, which results in the inhibitio n of GABA release.