PHENYLEPHRINE SUPPRESSES OUTWARD K+ CURRENTS IN RAT ATRIAL MYOCYTES

The modulation of whole cell K+ currents by the alpha(1)-adrenergic ag onist, phenylephrine, was studied in isolated rat atrial myocytes by u se of perforated-patch whole cell recording techniques. The outward K current in these myocytes consists of two inactivating components (i( K,f), and i(K,s)), which differ in the kinetics of inactivation and re covery from inactivation, and a noninactivating component, (i(K,ss)). Superfusion of these myocytes with 10 mu M phenylephrine caused a rapi d suppression of i(K,ss), with little effect on the other current comp onents. This effect of phenylephrine could be mimicked by exogenous ap plication of 1,2-dioctanoyl-sn-glycerol (20 mu M), a membrane-permeant diacylglycerol analogue; however, it was clearly distinct from the ef fect of 5 nM, alpha-dendrotoxin, which selectively suppressed the slow ly inactivating current component, i(K,s), while having no effect on i (K,ss). At a dose of 50 mu M phenylephrine also suppressed i(K,s). The re was no significant effect of phenylephrine (10 or 50 mu M) or alpha -dendrotoxin (5 nM) on the rapidly inactivating current component, i(K ,f). The kinetic and pharmacological differences between these current components suggest that they represent the activity of distinct K+ ch annels.