Low sodium inotropy is accompanied by diastolic Ca 2+ gain and systolic loss in isolated guinea-pig ventricular myocytes

Abstract : We measured sarcolemmal Ca2+ fluxes responsible for the positive inotropic effects of solutions with reduced Na+ concentration in voltage-clamped guinea-pig ventricular myocytes; intracellular Ca2+ concentration ([Ca2+]i) was measured with Indo-1. Reduction of external Na+ concentration by 50 % (to 67 mM) produced an increase in systolic [Ca2+]i accompanied by a decrease in Ca2+ entry via the L-type Ca2+ current. With reduced Na+ concentration, there was an initial decrease in the Na+-Ca2+ exchange current on repolarization followed by an increase to greater than control. We attribute this initial decrease to a decrease in the Na+ gradient and the subsequent increase to a fall in intracellular Na+ concentration and increase in systolic [Ca2+]i. The decreased L-type Ca2+ current and increased Ca2+ efflux on Na+-Ca2+ exchange resulted in a calculated systolic loss of Ca2+. The calculated systolic loss of Ca2+ was accompanied by a measured increase in sarcoplasmic reticulum (SR) Ca2+ content. Reduction of the external Na+ concentration also produced an outward shift of holding current which was blocked by Ni2+. This is taken to represent Ca2+ influx via Na+-Ca2+ exchange. When diastolic influx is taken into account, the observed gain in SR Ca2+ content can be predicted. The measurements show that, in reduced Na+, much of the entry of Ca2+ into the cell occurs during diastole (via Na+-Ca2+ exchange) rather than in systole (via the L-type Ca2+ current).
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William Même, S. O'Neill, D. Eisner. Low sodium inotropy is accompanied by diastolic Ca 2+ gain and systolic loss in isolated guinea-pig ventricular myocytes. Journal of Physiology, Wiley, 2001, 530 (3), pp.487-495. ⟨10.1111/j.1469-7793.2001.0487k.x⟩. ⟨hal-02149116⟩

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