PROTEIN-KINASE-C ACTIVATION ENHANCES THE DELAYED RECTIFIER POTASSIUM CURRENT IN GUINEA-PIG HEART-CELLS

The possible involvement of protein kinase C in modulating membrane currents was investigated in isolated guinea-pig ventricular cells. In a Na+- and K+-free external solution, the delayed rectifier K+ current (IK) was increased by the activator of protein kinase C (PKC), 12-O-tetradecanoylphorbol-13-acetate (TPA). The amplitude of the IK tail elicited by a return from a depolarizing pulse for 3 s at +50 mV to a holding potential of -30 mV was increased by 32±4% (mean±s.e., n=6) after the external application of 1 nm TPA, and by 60±17% (n=5) after 10nm. The increase in IK produced by 1 nm TPA was abolished by the inhibitor of PKC, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7, 10 μm). In addition, the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol (OAG, 125 μm) also increased IK (58±9%, n=3). PKC purified from bovine brain remarkably increased IK (151±101%, n=5) in the presence of 1 nm TPA when it was internally applied using the cell dialysis method. The concentration-response curve of IK for the intracellular concentration of Ca2+ was shifted to the left by 1 nm TPA, suggesting a Ca2+-dependent action of PKC and/or altered Ca2+-sensitivity of IK channels by phosphorylation. On the other hand, 1 nm TPA had no substantial influence on the Ca2+ current (decreased by 7±4%, n=5) or the inward-rectifier K+ current (decreased by 5±5% in outward component, and 3±8% in inward component, n=6). Therefore, the action of PKC was to specifically increase IK without affecting the other two currents. © 1990.