Reversal of mitochondrial Na/Ca exchange during metabolic inhibition in rat cardiomyocytes.
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 (delta psi(m)) 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. Delta psi(m) was determined using rhodamine 123. Following metabolic inhibition, [Ca2+]m was significantly lower in Na-depleted cells than controls (P<0.001), [Ca2+]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 delta psi(m) during metabolic inhibition is consistent with inactivity of the Ca-uniporter.
Bristol Heart Institute, Bristol Royal Infirmary, University of Bristol, UK. elinor. griffiths@bristol.ac.uk
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Griffiths
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D002135:Calcium-Binding Proteins / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002469:Cell Separation; D003593:Cytoplasm / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; C034703:mitochondrial calcium uniporter; D012964:Sodium; D002118:Calcium