Activation of protein kinase C differentially modulates neuronal Na+, Ca2+, and gamma-aminobutyrate type A channels.
Xenopus oocytes were used to study the interaction of neuronal quisqualate receptors with neuronal ion channels. Total mRNA was isolated from chick forebrain and injected into Xenopus oocytes. This technique led to the expression of functional voltage-gated Na+ and Ca2+ channels, of ligand-gated gamma-aminobutyrate and kainate receptor channels, and of quisqualate receptors that could activate endogenous chloride channels by means of inositol trisphosphate-mediated Ca2+ release. Exposure of the oocytes to quisqualate decreased the amplitude of the Na+ current and of the gamma-aminobutyrate type A-gated current and increased the amplitude of the Ba2+ current through Ca2+ channels. This modulation of neuronal ion channels by quisqualate could be mimicked by the protein kinase C activator phorbol 12-myristate 13-acetate and the diacylglycerol analogue 1,2-oleoylacetylglycerol. The kainate-gated channel was not affected by these agents. Phorbol esters that do not activate protein kinase C, alpha-phorbol 12-myristate 13-acetate and alpha-phorbol, were without effect. The inhibitor of protein kinase C, tamoxifen, prevented the modulatory effects of phorbol 12-myristate 13-acetate. The present evidence suggests that the activity of the neuronal Na+ and Ca2+ channels and the ligand-gated gamma-aminobutyrate type A receptor channel are under the control of protein kinase C and that neurotransmitters that activate protein kinase C could profoundly affect neuronal signaling.
Sigel
E
E
Pharmakologisches Institut, Universität Bern, Switzerland.
Baur
R
R
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002645:Chickens; D004789:Enzyme Activation; D007473:Ion Channels / Q000502:physiology*; D010069:Oxadiazoles / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D016318:Quisqualic Acid; D011963:Receptors, GABA-A / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014981:Xenopus
D007473:Ion Channels; D010069:Oxadiazoles; D011963:Receptors, GABA-A; D013629:Tamoxifen; D016318:Quisqualic Acid; D012964:Sodium; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium