부산대학교 도서관

Previous studies showed that myocardial Na+ overload during ischemia directly induced mitochondrial damage. The pathway for Na+ flux into mitochondria remains unclear. We examined possible routes for Na+ flux into mitochondria in the ischemic heart. Isolated perfused rat hearts were subjected to 15- to 35-min ischemia followed by 60-min reperfusion and then Na+ content and respiratory function in mitochondria of the ischemic heart were determined. The mitochondrial Na+ content of the ischemic heart was ischemic duration-dependently increased, associated with a reduction in mitochondrial respiratory function. To mimic induction of mitochondrial Na+ overload in vitro, isolated mitochondria were incubated with 6.25 to 50 mM NaCl or sodium lactate, a metabolite of anaerobic glycolysis, in the presence and absence of a mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 and a monocarboxylate transporter (MCT) inhibitor α-cyano-4-hydroxy cinnamic acid (CHCA). Incubation of mitochondria with NaCl or sodium lactate increased the mitochondrial Na+ concentration. This increase in mitochondrial Na+ was partially attenuated by the presence of either inhibitor. Combined treatment of mitochondria with both inhibitors attenuated sodium lactate-induced increase in Na+ content to a greater degree than that treated with either agent. These results suggest that mitochondrial Na+/Ca2+ exchanger and MCT inhibitor-sensitive Na+ transporter are possible pathways for the mitochondrial Na+ overload in the ischemic myocardium.