Ruthenium red inhibits mitochondrial Na+ and K+ uniports induced by magnesium removal.
Removal of bound magnesium from the outer surface of the inner mitochondrial membrane opens up a Na+ and Li+ selective electrophoretic uniport pathway whereas simultaneous depletion of intramitochondrial magnesium induces an electrogenic K+ flux as well. In order to clarify the nature of these cation movements we tested the effect of ruthenium red, a potent and specific inhibitor of the mitochondrial Ca2+ uniporter on different Na+ and K+ uniport-associated phenomena. Ruthenium red efficiently inhibited mitochondrial swelling and depolarization induced by either EDTA in a NaCl-based medium (Na+ uniport) or by EDTA plus A23187 in a KCl-based medium (K+ uniport). For both cation uniports half-maximal inhibition was attained at a ruthenium red concentration as low as 40 nM. Complete inhibition was found above 200 nM. Neither the Na+/H+ nor the K+/H+ exchange was affected by ruthenium red. In light of these observations the possibility is raised that the electrogenic Na+ and K+ fluxes provoked by magnesium reduction or depletion may be mediated through the Ca2+ uniporter. It is suggested that intactness of the mitochondrial magnesium pools is necessary for maintaining the Ca2+ selectivity of the Ca2+ uniporter, and alterations of the membrane-associated magnesium content would make this transport route available also for monovalent cations.
Department of Physiology, Semmelweis University Medical School, Budapest, Hungary.
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Kapus
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Szászi
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Káldi
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Ligeti
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Fonyó
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D014634:Valinomycin / Q000494:pharmacology
D012430:Ruthenium Red; D014634:Valinomycin; D000001:Calcimycin; D004492:Edetic Acid; D012964:Sodium; D008274:Magnesium; D011188:Potassium