MODULATION OF HIPPOCAMPAL GLYCINE RECEPTOR CHANNELS BY PROTEIN-KINASE-C

THE inhibitory glycine receptor (GlyR) is composed of polypeptide subu nits that contain intracellular consensus sequences for phosphorylatio n by protein kinase C (PKC). During whole-cell recording from rat hipp ocampal neurones, we observed a time-dependent increase of the glycine -induced membrane current. After 22 min the amplitude was 260 + 13% of the initial control response. PRC was involved in the modulation of h ippocampal glycine receptors, since the observed effect was more promi nent when the phorbol ester PMA, an activator of PKC, was included in the patch pipette. The action of PMA was mimicked by applying the 5-HT , receptor agonist, alpha-methyl-serotonin, to the cells. The time-dep endent increase in glycine responses was reduced by either tamoxifen, an inhibitor of PKC, or by alkaline phosphatase. Protein kinase A and tyrosine kinase were not involved as modulatory drugs of these kinases had no effect. These results provide direct evidence for the regulati on of GlyR function by PKC in rat hippocampal neurones.