Phenylephrine suppresses outward K+ currents in rat atrial myocytes.
The modulation of whole cell K+ currents by the alpha 1-adrenergic agonist, phenylephrine, was studied in isolated rat atrial myocytes by use of perforated-patch whole cell recording techniques. The out ward K+ current in these myocytes consists of two inactivating components (iK,f and iK,s), which differ in the kinetics of inactivation and recovery from inactivation, and a noninactivating component, (iK,ss). Superfusion of these myocytes with 10 microM phenylephrine caused a rapid suppression of iK,ss, with little effect on the other current components. This effect of phenylephrine could be mimicked by exogenous application of 1,2-dioctanoyl-sn-glycerol (20 microM), a membrane-permeant diacylglycerol analogue; however, it was clearly distinct from the effect of 5 nM alpha-dendrotoxin, which selectively suppressed the slowly inactivating current component, iK,s, while having no effect on iK,ss. At a dose of 50 microM, phenylephrine also suppressed iK,s. There was no significant effect of phenylephrine (10 or 50 microM) or alpha-dendrotoxin (5 nM) on the rapidly inactivating current component, iK,f. The kinetic and pharmacological differences between these current components suggest that they represent the activity of distinct K+ channels.
Van Wagoner
D R
DR
Department of Molecular Cardiology, Cleveland Clinic Foundation, Ohio 44195-5069, USA. vanwagd@cesmtp.ccf.org
Kirian
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M
Lamorgese
M
M
D000818:Animals; D016275:Atrial Function / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000494:pharmacology; D004553:Electric Conductivity; D008297:Male; D009206:Myocardium / Q000166:cytology; D009498:Neurotoxins / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004546:Elapid Venoms; D009498:Neurotoxins; D010656:Phenylephrine; C020273:dendrotoxin; D011188:Potassium