Ouabain increases myofibrillar Ca2+ sensitivity but does not influence the Ca2+ release in human skinned fibres

Abstract

The present study investigated the impact of the Na+ pump inhibitor ouabain (g-strophanthin) on Ca2+ sensitivity and Ca2+ release in human right auricular trabeculae (coronary bypass) and in skinned muscle fibres from left ventricular myocardium (cardiac transplantation, dilated cardiomyopathy). A time-dependent increase in force of contraction was observed in right auricular trabeculae in response to ouabain (100 nM) before the intracellular Ca2+ transient (fura-2) increased (n=6). In triton X-skinned fibres (no sarcoplasmic reticulum) of human failing myocardium, ouabain (1–100 nM) concentration-dependently increased tension at a free extracellular Ca2+ concentration of 1 μM and the Hill coefficient of the Ca2+-dependent tension development. Ouabain (1–100 nM) did not directly induce a Ca2+ release out of the sarcoplasmic reticulum, nor did it alter the caffeine (10 mM) induced sarcoplasmic reticulum Ca2+ release in saponin-skinned fibre preparations in which the sarcoplasmic reticulum had been Ca2+-loaded.In conclusion, ouabain increases myofibrillar Ca2+ sensitivity possibly due to an increase in the cooperativity of the thick and thin myofilaments. This mechanism may additionally contribute to the positive inotropic effect of ouabain.