Involvement of Protein Kinase C in Ethanol‐Induced Inhibition of NMDA Receptor Function in Cerebellar Granule Cells

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Abstract
Ethanol inhibits N‐methyl‐d‐aspartate (NMDA)‐stimulated increases in intracellular Ca2+ in cerebellar granule cells apparently by reducing the 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 the protein kinase inhibitors, staurosporine and calphostin C. We previously showed that activation of protein kinase C in cerebellar granule cells also resulted in inhibition of the NMDA response, and in decreased potency of glycine at the NMDA receptor. Furthermore, the inhibitory effects of ethanol and protein kinase C activation are not additive. These results suggest a role for protein kinase C in ethanol inhibition of NMDA responses in cerebellar granule cells. In contrast, although ethanol can inhibit the response to kainate in these cells in a “competitive” manner, this response is not affected by activation of protein kinase C.