Low sodium inotropy is accompanied by diastolic Ca2+ gain and systolic loss in isolated guinea‐pig ventricular myocytes

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Abstract
1 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. 2 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. 3 The decreased L-type Ca2+ current and increased Ca2+ efflux on Na+-Ca2+ exchange resulted in a calculated systolic loss of Ca2+. 4 The calculated systolic loss of Ca2+ was accompanied by a measured increase in sarcoplasmic reticulum (SR) Ca2+ content. 5 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. 6 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).