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. 1990 Mar 1;266(2):329–334. doi: 10.1042/bj2660329

Manganese and calcium efflux kinetics in brain mitochondria. Relevance to manganese toxicity.

C E Gavin 1, K K Gunter 1, T E Gunter 1
PMCID: PMC1131135  PMID: 2317189

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allshire A., Bernardi P., Saris N. E. Manganese stimulates calcium flux through the mitochondrial uniporter. Biochim Biophys Acta. 1985 May 3;807(2):202–209. doi: 10.1016/0005-2728(85)90123-9. [DOI] [PubMed] [Google Scholar]
  2. Archibald F. S., Fridovich I. The scavenging of superoxide radical by manganous complexes: in vitro. Arch Biochem Biophys. 1982 Apr 1;214(2):452–463. doi: 10.1016/0003-9861(82)90049-2. [DOI] [PubMed] [Google Scholar]
  3. Archibald F. S., Tyree C. Manganese poisoning and the attack of trivalent manganese upon catecholamines. Arch Biochem Biophys. 1987 Aug 1;256(2):638–650. doi: 10.1016/0003-9861(87)90621-7. [DOI] [PubMed] [Google Scholar]
  4. Autissier N., Rochette L., Dumas P., Beley A., Loireau A., Bralet J. Dopamine and norepinephrine turnover in various regions of the rat brain after chronic manganese chloride administration. Toxicology. 1982;24(2):175–182. doi: 10.1016/0300-483x(82)90055-5. [DOI] [PubMed] [Google Scholar]
  5. Beatrice M. C., Stiers D. L., Pfeiffer D. R. Increased permeability of mitochondria during Ca2+ release induced by t-butyl hydroperoxide or oxalacetate. the effect of ruthenium red. J Biol Chem. 1982 Jun 25;257(12):7161–7171. [PubMed] [Google Scholar]
  6. Becker G. L. Steady state regulation of extramitochondrial Ca2+ by rat liver mitochondria: effects of Mg2+ and ATP. Biochim Biophys Acta. 1980 Jul 8;591(2):234–239. doi: 10.1016/0005-2728(80)90155-3. [DOI] [PubMed] [Google Scholar]
  7. CHANCE B. THE ENERGY-LINKED REACTION OF CALCIUM WITH MITOCHONDRIA. J Biol Chem. 1965 Jun;240:2729–2748. [PubMed] [Google Scholar]
  8. Cawte J., Hams G., Kilburn C. Manganism in a neurological ethnic complex in Northern Australia. Lancet. 1987 May 30;1(8544):1257–1257. doi: 10.1016/s0140-6736(87)92699-7. [DOI] [PubMed] [Google Scholar]
  9. Chance B., Mela L. Calcium and manganese interactions in mitochondrial ion accumulation. Biochemistry. 1966 Oct;5(10):3220–3223. doi: 10.1021/bi00874a022. [DOI] [PubMed] [Google Scholar]
  10. Cobbold P. H., Rink T. J. Fluorescence and bioluminescence measurement of cytoplasmic free calcium. Biochem J. 1987 Dec 1;248(2):313–328. doi: 10.1042/bj2480313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dastur D. K., Manghani D. K., Raghavendran K. V. Distribution and fate of 54Mn in the monkey: studies of differnnt parts of the central nervous system and other organs. J Clin Invest. 1971 Jan;50(1):9–20. doi: 10.1172/JCI106487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dipolo R., Marty A. Measurement of Na-K pump current in acinar cells of rat lacrimal glands. Biophys J. 1989 Mar;55(3):571–574. doi: 10.1016/S0006-3495(89)82850-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Donaldson J. The physiopathologic significance of manganese in brain: its relation to schizophrenia and neurodegenerative disorders. Neurotoxicology. 1987 Fall;8(3):451–462. [PubMed] [Google Scholar]
  14. Fahn S. Biochemistry of the basal ganglia. Adv Neurol. 1976;14:59–89. [PubMed] [Google Scholar]
  15. Ferraz H. B., Bertolucci P. H., Pereira J. S., Lima J. G., Andrade L. A. Chronic exposure to the fungicide maneb may produce symptoms and signs of CNS manganese intoxication. Neurology. 1988 Apr;38(4):550–553. doi: 10.1212/wnl.38.4.550. [DOI] [PubMed] [Google Scholar]
  16. Graham D. G. Catecholamine toxicity: a proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson's disease. Neurotoxicology. 1984 Spring;5(1):83–95. [PubMed] [Google Scholar]
  17. Gunter R. E., Puskin J. S., Russell P. R. Quantitative magnetic resonance studies of manganese uptake by mitochondria. Biophys J. 1975 Apr;15(4):319–333. doi: 10.1016/S0006-3495(75)85822-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gunter T. E., Chace J. H., Puskin J. S., Gunter K. K. Mechanism of sodium independent calcium efflux from rat liver mitochondria. Biochemistry. 1983 Dec 20;22(26):6341–6351. doi: 10.1021/bi00295a046. [DOI] [PubMed] [Google Scholar]
  19. Gunter T. E., Rosier R. N., Tucker D. A., Gunter K. K. Uptake of calcium and manganese by rat liver submitochondrial particles. Ann N Y Acad Sci. 1978 Apr 28;307:246–247. doi: 10.1111/j.1749-6632.1978.tb41954.x. [DOI] [PubMed] [Google Scholar]
  20. Halliwell B. Manganese ions, oxidation reactions and the superoxide radical. Neurotoxicology. 1984 Spring;5(1):113–117. [PubMed] [Google Scholar]
  21. Hayat L. H., Crompton M. Evidence for the existence of regulatory sites for Ca2+ on the Na+/Ca2+ carrier of cardiac mitochondria. Biochem J. 1982 Feb 15;202(2):509–518. doi: 10.1042/bj2020509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hughes B. P., Exton J. H. Effect of micromolar concentrations of manganese ions on calcium-ion cycling in rat liver mitochondria. Biochem J. 1983 Jun 15;212(3):773–782. doi: 10.1042/bj2120773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Konji V., Montag A., Sandri G., Nordenbrand K., Ernster L. Transport of Ca2+ and Mn2+ by mitochondria from rat liver, heart and brain. Biochimie. 1985 Dec;67(12):1241–1250. doi: 10.1016/s0300-9084(85)80133-4. [DOI] [PubMed] [Google Scholar]
  24. Kröner H. The real kinetics of the mitochondrial calcium uniporter of the liver and its role in cell calcium regulation. Biol Chem Hoppe Seyler. 1988 Mar;369(3):149–155. [PubMed] [Google Scholar]
  25. Liccione J. J., Maines M. D. Selective vulnerability of glutathione metabolism and cellular defense mechanisms in rat striatum to manganese. J Pharmacol Exp Ther. 1988 Oct;247(1):156–161. [PubMed] [Google Scholar]
  26. MAYNARD L. S., COTZIAS G. C. The partition of manganese among organs and intracellular organelles of the rat. J Biol Chem. 1955 May;214(1):489–495. [PubMed] [Google Scholar]
  27. Nicholls D. G., Crompton M. Mitochondrial calcium transport. FEBS Lett. 1980 Mar 10;111(2):261–268. doi: 10.1016/0014-5793(80)80806-4. [DOI] [PubMed] [Google Scholar]
  28. Olafsdottir K., Pascoe G. A., Reed D. J. Mitochondrial glutathione status during Ca2+ ionophore-induced injury to isolated hepatocytes. Arch Biochem Biophys. 1988 May 15;263(1):226–235. doi: 10.1016/0003-9861(88)90631-5. [DOI] [PubMed] [Google Scholar]
  29. Puskin J. S., Gunter T. E., Gunter K. K., Russell P. R. Evidence for more than one Ca2+ transport mechanism in mitochondria. Biochemistry. 1976 Aug 24;15(17):3834–3842. doi: 10.1021/bi00662a029. [DOI] [PubMed] [Google Scholar]
  30. Roels H., Lauwerys R., Buchet J. P., Genet P., Sarhan M. J., Hanotiau I., de Fays M., Bernard A., Stanescu D. Epidemiological survey among workers exposed to manganese: effects on lung, central nervous system, and some biological indices. Am J Ind Med. 1987;11(3):307–327. doi: 10.1002/ajim.4700110308. [DOI] [PubMed] [Google Scholar]
  31. Suzuki Y., Mouri T., Suzuki Y., Nishiyama K., Fujii N. Study of subacute toxicity of manganese dioxide in monkeys. Tokushima J Exp Med. 1975 Sep;22:5–10. [PubMed] [Google Scholar]
  32. Unitt J. F., McCormack J. G., Reid D., MacLachlan L. K., England P. J. Direct evidence for a role of intramitochondrial Ca2+ in the regulation of oxidative phosphorylation in the stimulated rat heart. Studies using 31P n.m.r. and ruthenium red. Biochem J. 1989 Aug 15;262(1):293–301. doi: 10.1042/bj2620293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Vainio H., Mela L., Chance B. Energy dependent bivalent cation translocation in rat liver mitochondria. Eur J Biochem. 1970 Feb;12(2):387–391. doi: 10.1111/j.1432-1033.1970.tb00863.x. [DOI] [PubMed] [Google Scholar]
  34. Vinogradov A., Scarpa A. The initial velocities of calcium uptake by rat liver mitochondria. J Biol Chem. 1973 Aug 10;248(15):5527–5531. [PubMed] [Google Scholar]
  35. Wingrove D. E., Gunter T. E. Kinetics of mitochondrial calcium transport. I. Characteristics of the sodium-independent calcium efflux mechanism of liver mitochondria. J Biol Chem. 1986 Nov 15;261(32):15159–15165. [PubMed] [Google Scholar]

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