Protein kinase C activation in human ventricular myocardium

We investigated the effects of 12-deoxyphorbol 13 isobutyrate 20 acetate (DPBA) on contractile function and intracellular calcium handling in normal human ventricular myocardium. The activation of protein kinase C by DPBA resulted in a decrease in sarcoplasmic reticulum calcium release and a reduction in isometric twitch. Force-calcium relationships were obtained by tetanizing intact muscles or by chemically skinning muscle fibers. These relationships were fitted to a modified Hill function. In intact preparations, DPBA shifted the force-calcium relationship towards higher intracellular calcium concentrations by 0.12 μM (n = 5) and maximal force production was decreased 45.5 ± 6.1%. These experiments show that protein kinase C activation affects intracellular calcium availability and myofibrillar calcium responsiveness.