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Involvement of Protein Kinase C in Ethanol‐Induced Inhibition of NMDA Receptor Function in Cerebellar Granule Cells
Author(s) -
Snell Lawrence D.,
Tabakoff Boris,
Hoffman Paula L.
Publication year - 1994
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1994.tb00884.x
Subject(s) - nmda receptor , kainate receptor , staurosporine , protein kinase c , chemistry , protein kinase a , calphostin , biochemistry , microbiology and biotechnology , cerebellum , biology , kinase , receptor , ampa receptor , endocrinology
Ethanol inhibits N ‐methyl‐ d ‐aspartate (NMDA)‐stimulated increases in intracellular Ca 2+ 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.