title: Manganese and calcium efflux kinetics in brain mitochondria. Relevance to manganese toxicity.
abstract: Manganese shares the uniport mechanism of mitochondrial calcium influx, accumulates in mitochondria and is cleared only very slowly from brain. Using dual-label isotope techniques, we have investigated both Mn2+ and Ca2+ mitochondrial efflux kinetics. We report that (1) there is no significant Na(+)-dependent Mn2+ efflux from brain mitochondria; (2) Mn2+ inhibits both Na(+)-dependent and Na(+)-independent Ca2+ efflux in brain, in a mode that appears to be primarily competitive and with apparent Ki values of 5.1 and 7.9 nmol/mg respectively; and (3) Ca2+ does not appear to inhibit Mn2+ efflux from brain mitochondria. Findings (1) and (2) suggest the possibility of mitochondrial accumulation of both Mn2+ and Ca2+ in Mn2(+)-intoxicated brain.
authors.affiliation: University of Rochester Medical Center, NY 14642.
authors.forename: C E
authors.initials: CE
authors.lastname: Gavin
authors.forename: K K
authors.initials: KK
authors.lastname: Gunter
authors.forename: T E
authors.initials: TE
authors.lastname: Gunter
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008345:Manganese / Q000494:pharmacology*; D020149:Manganese Poisoning; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology
chemical_list: D008345:Manganese; D012964:Sodium; D002118:Calcium