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

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 Ca-45 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 Ca-45 uptake in 5 mM KCl was slightly increased by a low concentration of TPA (10(-9) M), but high K-induced Ca-45 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 Ca-45 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.