Protein kinase C activation in human ventricular myocardium

Article type: Research Article

Authors: Gwathmey, Judith K.^a | Hajjar, Roger J.^b

Affiliations: [a] Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory of Beth Israel Hospital, Department of Medicine, Cardiovascular Division, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts, 02215, USA | [b] Harvard Medical School-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA

Note: [] Accepted by: Editor J.-F. Stoltz

Abstract: We investigated the effects of l2-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.

Keywords: human, phorbol ester, calcium, myocardium

DOI: 10.3233/BIR-1991-283-406

Journal: Biorheology, vol. 28, no. 3-4, pp. 151-160, 1991