K201 improves aspects of the contractile performance of human failing myocardium via reduction in Ca2+ leak from the sarcoplasmic reticulum.

ABSTRACT: In heart failure, intracellular Ca2+ leak from cardiac ryanodine receptors (RyR2s) leads to a loss of Ca2+ from the sarcoplasmic reticulum (SR) potentially contributing to decreased function. Experimental data suggest that the 1,4-benzothiazepine K201 (JTV-519) may stabilise RyR2s and thereby reduce detrimental intracellular Ca2+ leak. Whether K201 exerts beneficial effects in human failing myocardium is unknown. Therefore, we have studied the effects of K201 on muscle preparations from failing human hearts. K201 (0.3 microM; extracellular [Ca2+]e 1.25 mM) showed no effects on contractile function and micromolar concentrations resulted in negative inotropic effects (K201 1 microM; developed tension -9.8 +/- 2.5% compared to control group; P < 0.05). Interestingly, K201 (0.3 microM) increas

SUBMITTER: Toischer K 

PROVIDER: S-EPMC2807967 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature