Activation of protein kinase C inhibits kainate-induced currents in oocytes expressing glutamate receptor subunits.
The effect of protein kinase C (PKC) activation on maximal kainate (KA)-induced currents was studied in Xenopus oocytes expressing the glutamate receptor (GluR) subunits GluR3, GluR1 + 3, GluR2 + 3, and GluR6. The PKC activator phorbol 12-myristate 13-acetate (PMA) inhibited peak KA responses in a time-dependent manner. The magnitude of inhibition was greatest in GluR6-expressing oocytes. Desensitizing KA currents characterized by a peak, transient current followed by a slower, desensitizing current were observed in oocytes expressing GluR3 and GluR1 + 3 receptors. PMA inhibited the desensitization, and this effect could be observed before PMA's inhibition of peak current amplitude. PMA-mediated inhibition of both desensitization and peak current amplitude was prevented by intracellular injection of the protein kinase C (PKC) inhibitor peptide. These results suggest that the function of GluRs is regulated by PKC-dependent phosphorylation.
Dildy-Mayfield
J E
JE
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Harris
R A
RA
D000818:Animals; D004553:Electric Conductivity; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014982:Xenopus laevis
D017470:Receptors, Glutamate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D007608:Kainic Acid