Wortmannin inhibits the myofilament Ca2+ sensitization induced by endothelin-1

Endothelin-1 induces a positive inotropic effect due to a combination of an increase in Ca2+ transients and myofilament Ca2+ sensitivity in rabbit ventricular myocardium. We carried out the experiments to examine the potential contribution of myosin light chain kinase to the Ca2+ sensitization induced by endothelin-1 by use of wortmannin that inhibits myosin light chain kinase at high concentrations (IC50=200 nM). Wortmannin at 3 muM suppressed the basal force of contraction. but did not affect the positive inotropic effect mediated by beta-adrenoceptors. Wortmannin at 1 and 3 muM markedly inhibited the positive inotropic effect of endothelin-1, but did not affect the increase in Ca2+ transients elicited by endothelin-1. The present Findings imply that the increase in myofilamem Ca2+ sensitivity induced by endothelin-1 may be in part due to activation of myosin light chain kinase in rabbit ventricular myocardium. (C) 2004 Elsevier B.V. All rights reserved.