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 microM (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.
Charles A. Dana Research Institute, Boston, Massachusetts.
J K
JK
Gwathmey
R J
RJ
Hajjar
D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000201:enzymology; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*
D010703:Phorbol Esters; C047907:12-deoxyphorbol-13-isobutyrate-20-acetate; D011493:Protein Kinase C; D002118:Calcium