INVOLVEMENT OF PROTEIN-KINASE-C IN ETHANOL-INDUCED INHIBITION OF NMDARECEPTOR FUNCTION IN CEREBELLAR GRANULE CELLS

Ethanol inhibits N-methyl-D-aspartate (NMDA)-stimulated increases in i ntracellular Ca2+ in cerebellar granule cells apparently by reducing t he potency of glycine to act as a co-agonist at the NMDA receptor. The inhibitory effect of ethanol on the NMDA response in these cells can be reversed not only by a high concentration of glycine, but also by t he protein kinase inhibitors, staurosporine and calphostin C. We previ ously showed that activation of protein kinase C in cerebellar granule cells also resulted in inhibition of the NMDA response, and in decrea sed potency of glycine at the NMDA receptor. Furthermore, the inhibito ry effects of ethanol and protein kinase C activation are not additive . These results suggest a role for protein kinase C in ethanol inhibit ion of NMDA responses in cerebellar granule cells. In contrast, althou gh ethanol can inhibit the response to kainate in these cells in a ''c ompetitive'' manner, this response is not affected by activation of pr otein kinase C.