ALPHA-1-ADRENOCEPTOR STIMULATION ENHANCES THE DELAYED RECTIFIER K+ CURRENT OF GUINEA-PIG VENTRICULAR CELLS THROUGH THE ACTIVATION OF PROTEIN-KINASE-C

The effect of alpha1-adrenoceptor stimulation on the delayed rectifier K+ current (I(K)) was examined in isolated guinea pig ventricular cells by use of the patch-clamp method. I(K) was evoked by a 3-second depolarizing pulse from a holding potential of -30 mV in a Na+- and K+-free solution containing 3 muM nifedipine. Phenylephrine (30 muM) in the presence of propranolol (1 muM) produced an increase in I(K). In five cells, phenylephrine increased the tail current Of I(K) by 23 +/- 5%. This effect of phenylephrine was blocked by prazosin (0.3 muM), a selective alpha1-blocker. Phenylephrine produced only a small effect on the voltage and time dependence Of I(K). Pretreatment with 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7, 10 muM) abolished the phenylephrine-induced increase in I(K). In addition, pretreatment with a maximally effective concentration of 12-O-tetradecanoylphorbol 13-acetate (100 nM) abolished the phenylephrine-induced increase in I(K). In conclusion, alpha1-adrenoceptor stimulation increases I(K) in guinea pig cardiomyocytes. This alpha1-adrenoceptor-mediated response may be related to an activation of protein kinase C. The increase in I(K) may explain a shortening or action potential duration observed after alpha1-adrenoceptor stimulation in guinea pig cells.