Receptor-coupled regulation of K+ channel N-type inactivation.
Phosphorylation of the inactivation gate of a K+ channel (Kv3.4) by protein kinase C (PKC) slows rapid N-type inactivation. To demonstrate that such an effect could occur under more physiological conditions, Kv3.4 and a metabotropic serotonin (5-HT) receptor were coexpressed in Xenopus oocytes. Application of 5-HT 10 microM to these oocytes produced two main effects: 1) Enhanced activity of endogenous Ca(++)-dependent Cl- channels; and 2) Kv3.4 currents exhibited significantly slower inactivation than the control currents (time constants at +50 mV: 7.1 +/- 0.6 ms and 14.7 +/- 3 ms, before and after 5-HT, respectively). These results are consistent with the presence of receptor-coupled activation of phospholipase C. 5-HT had little or no effect on Kv3.4 current kinetics when four N-terminal serines were mutated to alanine. Peak currents exhibited, however, a slow run-down. This study demonstrates that physiological activation of PKC may regulate K+ channel inactivation by a direct action.
Velasco
I
I
Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Philadelphia, PA 19107, USA.
Beck
E J
EJ
Covarrubias
M
M
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000502:physiology; D004553:Electric Conductivity; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D009154:Mutation; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D011985:Receptors, Serotonin / Q000378:metabolism* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D051670:Shaw Potassium Channels; D014981:Xenopus; D029867:Xenopus Proteins
D002712:Chlorides; C492016:KCNC4 protein, Xenopus; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011985:Receptors, Serotonin; D051670:Shaw Potassium Channels; D029867:Xenopus Proteins; D012701:Serotonin; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid