Dissociation of NAD(P)+-stimulated mitochondrial Ca2+ efflux from swelling and membrane damage.
NAD(P)+-stimulated Ca2+ efflux from mitochondria in a high-sucrose medium is irreversible and is accompanied by large-amplitude mitochondrial swelling and membrane damage. If sucrose is partially replaced by polyethylene glycol (Mr approximately equal to 1000) as osmolar supporting medium, Ca2+ efflux is still stimulated by NAD(P)+ but mitochondrial swelling is eliminated. Other experiments in a high-sucrose medium showed that the lag phase between NAD(P)H oxidation and the beginning of net Ca2+ efflux decreases with increasing temperature. At 37 degrees C Ca2+ efflux precedes mitochondrial swelling, even in a high-sucrose medium, showing that the mitochondrial damage, as reflected by large-amplitude swelling, is not obligatory for Ca2+ efflux induced by the oxidized state of mitochondrial NAD(P)+. If a high-sucrose medium is supplemented with 20 mM potassium acetate, longer periods of Ca2+ release can be observed before the appearance of swelling. Under these experimental conditions the release of Ca2+ can be completely reversed if the rereduction of NAD(P)+ is brought about by the addition of the reductants beta-hydroxybutyrate and isocitrate.
D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000502:physiology; D008930:Mitochondria, Liver / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009243:NAD / Q000502:physiology*; D010071:Oxaloacetates / Q000494:pharmacology; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature
D000085:Acetates; D010071:Oxaloacetates; D009243:NAD; D011092:Polyethylene Glycols; D019342:Acetic Acid; D002118:Calcium