Inhibitors of Na+/H+ and Na+/Ca2+ exchange depress intracellular calcium elevation induced by ischemia/reperfusion in rat cardiac myocytes

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Journal Title:
Volume 55, Issue 03, 2003
Key Word:
cardiac myocytes;ischemia/reperfusion;calcium;Na+/H+exchanger;sodium-calcium exchanger

Abstract: An increase in cytosolic free calcium has been shown to occur during ischemia in perfused hearts and plays a pivotal role in ischemia/reperfusion injury. The objective of this study was to investigate the contributions of Na+/H+exchange and Na+/Ca2+ exchange to changes in intracellular calcium ([Ca2+]i) during simulated ischemia and reperfusion in quiescent isolated rat cardiac myocytes. [Ca2+]i was measured by laser confocal microscope using the fluorescent indicator Fluo 3 and expressed as the corrected intensity of Fluo 3 fluorescence. [Ca2+]i increased to 140.3±13.0% (P<0.05 vs preischemic control 100%) after 5 min simulated ischemia, and remained at high level of 142.8±15.5% (P<0.05) after the following 15 min reperfusion. The increase in [Ca2+]i during simulated ischemia and reperfusion was suppressed by 100 μmol/L amiloride (inhibitor of Na+/H+exchanger), 5 mmol/L NiCl2 (inhibitor of Na+/Ca2+ exchanger) and calcium-free solution; [Ca2+]i was 101.4±16.3%, 110.4±11.1% and 107.1±10.8%, respectively, after 5 min simulated ischemia, and 97.8±14.3%, 106.2±14.5% and 106.6±15.7%, respectively, after 15 min reperfusion. Compared with control cells, the amplitude of spontaneous calcium oscillation was lessened in cells treated with Ca-free perfusion and NiCl2 during reperfusion. In addition, no calcium oscillation was observed in cells pretreated with amiloride. These results suggest that Na+/H+exchange and Na+/Ca2+ exchange are activated during simulated ischemia in isolated quiescent cardiac myocytes, leading to the elevation of [Ca2+]i induced by simulated ischemia and reperfusion.

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