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

• Published in: The Journal of physiology Vol. 530; no. 3; pp. 487 - 495
• Main Authors: Meme, W, O'Neill, S C, Eisner, DA
• Format: Journal Article
• Language: English
• Published: 01-02-2001
• ISSN: 0022-3751

We measured sarcolemmal Ca super(2+) fluxes responsible for the positive inotropic effects of solutions with reduced Na super(+) concentration in voltage-clamped guinea-pig ventricular myocytes; intracellular Ca super(2+) concentration ([Ca super(2+)] sub(i)) was measured with Indo-1. Reduction of external Na super(+) concentration by 50% (to 67 mM) produced an increase in systolic [Ca super(2+)] sub(i) accompanied by a decrease in Ca super(2+) entry via the L-type Ca super(2+) current. With reduced Na super(+) concentration, there was an initial decrease in the Na super(+)-Ca super(2+) exchange current on repolarization followed by an increase to greater than control. We attribute this initial decrease to a decrease in the Na super(+) gradient and the subsequent increase to a fall in intracellular Na super(+) concentration and increase in systolic [Ca super(2+)] sub(i). The decreased L-type Ca super(2+) current and increased Ca super(2+) efflux on Na super(+)-Ca super(2+) exchange resulted in a calculated systolic loss of Ca super(2+). The calculated systolic loss of Ca super(2+) was accompanied by a measured increase in sarcoplasmic reticulum (SR) Ca super(2+) content. Reduction of the external Na super(+) concentration also produced an outward shift of holding current which was blocked by Ni super(2+). This is taken to represent Ca super(2+) influx via Na super(+)-Ca super(2+) exchange. When diastolic influx is taken into account, the observed gain in SR Ca super(2+) content can be predicted. The measurements show that, in reduced Na super(+), much of the entry of Ca super(2+) into the cell occurs during diastole (via Na super(+)-Ca super(2+) exchange) rather than in systole (via the L-type Ca super(2+) current).