DOWN-REGULATION OF GLYCINE RECEPTOR CHANNELS BY PROTEIN-KINASE-C IN XENOPUS-OOCYTES INJECTED WITH SYNTHETIC RNA

Interaction of protein kinase C (PKC) with glycine receptor channels was examined using Xenopus oocytes expressing homomeric alpha glycine channels. 4 beta-Phorbol 12-myristate 13-acetate (4 beta-PMA), an activator of PKC, reduced the response to glycine; this effect was inhibited in the presence of staurosporine, a PKC inhibitor. By contrast, alpha-PMA, a poor PKC stimulant, did not affect the glycine currents. Thus, the PKC system is involved in negative-regulation of the glycine receptor channels. The results obtained from experiments with mutant receptors suggest that phosphorylation of the intracellular serine residue at 419 may relate to modification of the channel function.