Participation of PKC in modulation of the excitation-contraction process of chick embryo cardiac muscle.

Abstract

Phorbol esters are activators of protein kinase C (PKC) and have been widely used to study the function of this enzyme. We investigated the effect of phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), on tension responses and free cytosolic Ca in small strips of chick embryo ventricle and on the 45Ca influx in primary cultures of chick embryo ventricular cells. TPA (10(-8) M) decreased twitch tension about 40% when driven at 1 Hz. The free cytosolic Ca measured with fura-PE3 was rapidly increased in 110 mM KCl solution and this high K-induced increase was slightly inhibited by TPA (10(-8) M), by 12%. The resting 45Ca uptake in 5 mM KCl was slightly increased by a low concentration of TPA (10(-9) M), but high K-induced 45Ca uptake was decreased by TPA in a dose-dependent manner, but to 40% at the utmost. 4 alpha-Phorbol, an inactive phorbol ester, did not inhibit 45Ca uptake. These results indicate that TPA decreased the depolarization induced transsarcolemmal Ca uptake and thus the excitation-contraction process was attenuated, but to 40% at most. PKC may participate in the modulation of myocardial Ca homeostasis and contractile state.