Reversal of mitochondrial Na/Ca exchange during metabolic inhibition in rat cardiomyocytes

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Abstract
During hypoxia of isolated cardiomyocytes, Ca2+ entry into mitochondria may occur via the Na/Ca exchanger, the normal efflux pathway, and not the Ca‐uniporter, the normal influx route. If this is the case, then depletion of myocyte Na+ should inhibit Ca2+ uptake, and collapse of the mitochondrial membrane potential (Δψm) would inhibit the uniporter. To test these hypotheses, isolated rat myocytes were exposed to metabolic inhibition, to mimic hypoxia, and [Ca2+]m and [Ca2+]c determined by selective loading of indo‐1 into these compartments. Δψm was determined using rhodamine 123. Following metabolic inhibition, [Ca2+]m was significantly lower in Na‐depleted cells than controls (P2+]c was approximately the same in both groups, and mitochondria depolarised completely. Thus Na‐depletion inhibited mitochondrial Ca2+ uptake, suggesting that Ca2+ entry occurred via Na/Ca exchange, and the collapse of Δψm during metabolic inhibition is consistent with inactivity of the Ca‐uniporter.