Protein kinase C inhibits Kv1.1 potassium channel function.
The regulation by protein kinase C (PKC) of recombinant voltage-gated potassium (K) channels in frog oocytes was studied. Phorbol 12-myristate 13-acetate (PMA; 500 nM), an activator of PKC, caused persistent and large (up to 90%) inhibition of mouse, rat, and fly Shaker K currents. K current inhibition by PMA was blocked by inhibitors of PKC, and inhibition was not observed in control experiments with PMA analogs that do not activate PKC. However, site-directed substitution of potential PKC phosphorylation sites in the Kv1.1 protein did not prevent current inhibition by PMA. Kv1.1 current inhibition was also not accompanied by changes in macroscopic activation kinetics or in the conductance-voltage relationship. In Western blots, Kv1.1 membrane protein was not significantly reduced by PKC activation. The injection of oocytes with botulinum toxin C3 exoenzyme blocked the PMA inhibition of Kv1. 1 currents. These data are consistent with the hypothesis that PKC-mediated inhibition of Kv1.1 channel function occurs by a novel mechanism that requires a C3 exoenzyme substrate but does not alter channel activation gating or promote internalization of the channel protein.
Department of Physiology and Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA. bolan007@tc.umn.edu
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Boland
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Jackson
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology; D051662:Kv1.1 Potassium Channel; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009865:Oocytes; D010766:Phosphorylation; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000502:physiology; D011994:Recombinant Proteins; D051637:Shaker Superfamily of Potassium Channels; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014982:Xenopus laevis
D029721:Drosophila Proteins; C496947:Kcna1 protein, mouse; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D018048:Receptors, Purinergic P2; D011994:Recombinant Proteins; C496929:Sh protein, Drosophila; D051637:Shaker Superfamily of Potassium Channels; D051662:Kv1.1 Potassium Channel; D011493:Protein Kinase C; D001905:Botulinum Toxins; D013755:Tetradecanoylphorbol Acetate