a 1 - Adrenoceptor Stimulation Enhances the Delayed Rectifier K ' Current of Guinea Pig Ventricular Cells Through the Activation of Protein Kinase C

The effect of cal-adrenoceptor stimulation on the delayed rectifier K' current (IK) was examined in isolated guinea pig ventricular cells by use of the patch-clamp method. '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 ,uM nifedipine. Phenylephrine (30 ,uM) in the presence of propranolol (1 ELM) produced an increase in 'K. In five cells, phenylephrine increased the tail current of 'K by 23±5%. This effect of phenylephrine was blocked by prazosin (0.3 ,uM), a selective al-blocker. Phenylephrine produced only a small effect on the voltage and time dependence of IK. Pretreatment with 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7, 10 ,uM) abolished the phenylephrine-induced increase in IK. In addition, pretreatment with a maximally effective concentration of 12-O-tetradecanoylphorbol 13-acetate (100 nM) abolished the phenylephrine-induced increase in IK. In conclusion, a!,-adrenoceptor stimulation increases IK in guinea pig cardiomyocytes. This cvl-adrenoceptor-mediated response may be related to an activation of protein kinase C. The increase in IK may explain a shortening of action potential duration observed after ae-adrenoceptor stimulation in guinea pig cells. (Circulation Research 1992;71:1441-1446) KEYWoRDs * a,-adrenoceptors * delayed rectifier K' current * protein kinase C * cardiomyocytes phenylephrine * H-7 * patch clamp