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. 1981 Nov 15;200(2):379–388. doi: 10.1042/bj2000379

The alpha-adrenergic-mediated activation of Ca2+ influx into cardiac mitochondria. A possible mechanism for the regulation of intramitochondrial free CA2+.

P Kessar, M Crompton
PMCID: PMC1163546  PMID: 7340837

Abstract

Mitochondria isolated from rat hearts perfused with adrenaline, and from hearts excised from adrenaline-treated rats, showed an enhanced rate of respiration-dependent Ca2+ uptake. Adrenaline pretreatment did not change the activity of the Na+/Ca2+-antiporter of isolated heart mitochondria. Simultaneous measurements of the membrane potential revealed that perfusion with adrenaline has no significant effect on this parameter during Ca2+ accumulation. The activation of Ca2+ uptake was induced also by the alpha-adrenergic agonist, methoxamine, but not by the beta-adrenergic agonist, isoprenaline. Methoxamine pretreatment also increased the sensitivity of alpha-oxoglutarate dehydrogenase in intact mitochondria to 10 nM--300 nM extramitochondrial Ca2+ during steady-state Ca2+ recycling across the inner membrane. Possible implications of these data for the adrenergic regulation of oxidative metabolism are discussed.

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Selected References

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

  1. Akerman K. E. Changes in membrane potential during calcium ion influx and efflux across the mitochondrial membrane. Biochim Biophys Acta. 1978 May 10;502(2):359–366. doi: 10.1016/0005-2728(78)90056-7. [DOI] [PubMed] [Google Scholar]
  2. Benfey B. G., Varma D. R. Interactions of sympathomimetic drugs, propranolol and phentolamine, on atrial refractory period and contractility. Br J Pharmacol Chemother. 1967 Aug;30(3):603–611. doi: 10.1111/j.1476-5381.1967.tb02166.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Crompton M., Heid I. The cycling of calcium, sodium, and protons across the inner membrane of cardiac mitochondria. Eur J Biochem. 1978 Nov 15;91(2):599–608. doi: 10.1111/j.1432-1033.1978.tb12713.x. [DOI] [PubMed] [Google Scholar]
  4. Crompton M., Künzi M., Carafoli E. The calcium-induced and sodium-induced effluxes of calcium from heart mitochondria. Evidence for a sodium-calcium carrier. Eur J Biochem. 1977 Oct 3;79(2):549–558. doi: 10.1111/j.1432-1033.1977.tb11839.x. [DOI] [PubMed] [Google Scholar]
  5. Crompton M. The sodium ion/calcium ion cycle of cardiac mitochondria. Biochem Soc Trans. 1980 Jun;8(3):261–262. doi: 10.1042/bst0080261. [DOI] [PubMed] [Google Scholar]
  6. Denton R. M., McCormack J. G., Edgell N. J. Role of calcium ions in the regulation of intramitochondrial metabolism. Effects of Na+, Mg2+ and ruthenium red on the Ca2+-stimulated oxidation of oxoglutarate and on pyruvate dehydrogenase activity in intact rat heart mitochondria. Biochem J. 1980 Jul 15;190(1):107–117. doi: 10.1042/bj1900107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Denton R. M., McCormack J. G. On the role of the calcium transport cycle in heart and other mammalian mitochondria. FEBS Lett. 1980 Sep 22;119(1):1–8. doi: 10.1016/0014-5793(80)80986-0. [DOI] [PubMed] [Google Scholar]
  8. Dobson J. G., Jr, Ross J., Jr, Mayer S. E. The role of cyclic adenosine 3', 5'-monophosphate and calcium in the regulation of contractility and glycogen phosphorylase activity in guinea pig papillary muscle. Circ Res. 1976 Sep;39(3):388–395. doi: 10.1161/01.res.39.3.388. [DOI] [PubMed] [Google Scholar]
  9. George W. J., Wilkerson R. D., Kadowitz P. J. Influence of acetylcholine on contractile force and cyclic nucleotide levels in the isolated perfused rat heart. J Pharmacol Exp Ther. 1973 Jan;184(1):228–235. [PubMed] [Google Scholar]
  10. Govier W. C. Myocardial alpha adrenergic receptors and their role in the production of a positive inotropic effect by sympathomimetic agents. J Pharmacol Exp Ther. 1968 Jan;159(1):82–90. [PubMed] [Google Scholar]
  11. Hiraoka T., DeBuysere M., Olson M. S. Studies of the effects of beta-adrenergic agonists on the regulation of pyruvate dehydrogenase in the perfused rat heart. J Biol Chem. 1980 Aug 25;255(16):7604–7609. [PubMed] [Google Scholar]
  12. Kamo N., Muratsugu M., Hongoh R., Kobatake Y. Membrane potential of mitochondria measured with an electrode sensitive to tetraphenyl phosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state. J Membr Biol. 1979 Aug;49(2):105–121. doi: 10.1007/BF01868720. [DOI] [PubMed] [Google Scholar]
  13. Kuo J. F., Lee T. P., Reyes P. L., Walton K. G., Donnelly T. E., Jr, Greengard P. Cyclic nucleotide-dependent protein kinases. X. An assay method for the measurement of quanosine 3',5'-monophosphate in various biological materials and a study of agents regulating its levels in heart and brain. J Biol Chem. 1972 Jan 10;247(1):16–22. [PubMed] [Google Scholar]
  14. LaRaia P. J., Sonnenblick E. H. Autonomic control of cardiac C-AMP. Circ Res. 1971 Mar;28(3):377–384. doi: 10.1161/01.res.28.3.377. [DOI] [PubMed] [Google Scholar]
  15. Mayer S. E. Effect of catecholamines on cardiac metabolism. Circ Res. 1974 Sep;35 (Suppl 3):129–137. [PubMed] [Google Scholar]
  16. McCormack J. G., Denton R. M. The activation of pyruvate dehydrogenase in the perfused rat heart by adrenaline and other inotropic agents. Biochem J. 1981 Feb 15;194(2):639–643. doi: 10.1042/bj1940639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McCormack J. G., Denton R. M. The effects of calcium ions and adenine nucleotides on the activity of pig heart 2-oxoglutarate dehydrogenase complex. Biochem J. 1979 Jun 15;180(3):533–544. doi: 10.1042/bj1800533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moore C. L. Specific inhibition of mitochondrial Ca++ transport by ruthenium red. Biochem Biophys Res Commun. 1971 Jan 22;42(2):298–305. doi: 10.1016/0006-291x(71)90102-1. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Nicholls D. G., Scott I. D. The regulation of brain mitochondrial calcium-ion transport. The role of ATP in the discrimination between kinetic and membrane-potential-dependent calcium-ion efflux mechanisms. Biochem J. 1980 Mar 15;186(3):833–839. doi: 10.1042/bj1860833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nicholls D. G. The regulation of extramitochondrial free calcium ion concentration by rat liver mitochondria. Biochem J. 1978 Nov 15;176(2):463–474. doi: 10.1042/bj1760463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pfaff E., Klingenberg M., Heldt H. W. Unspecific permeation and specific exchange of adenine nucleotides in liver mitochondria. Biochim Biophys Acta. 1965 Jun 15;104(1):312–315. doi: 10.1016/0304-4165(65)90258-8. [DOI] [PubMed] [Google Scholar]
  23. Reuter H., Scholz H. The regulation of the calcium conductance of cardiac muscle by adrenaline. J Physiol. 1977 Jan;264(1):49–62. doi: 10.1113/jphysiol.1977.sp011657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rottenberg H., Scarpa A. Calcium uptake and membrane potential in mitochondria. Biochemistry. 1974 Nov 5;13(23):4811–4817. doi: 10.1021/bi00720a020. [DOI] [PubMed] [Google Scholar]
  25. Scarpa A., Azzone G. F. The mechanism of ion translocation in mitochondria. 4. Coupling of K+ efflux with Ca2+ uptake. Eur J Biochem. 1970 Feb;12(2):328–335. doi: 10.1111/j.1432-1033.1970.tb00854.x. [DOI] [PubMed] [Google Scholar]
  26. Schümann H. J., Endoh S., Brodde O. E. The time course of the effects of beta- and alpha-adrenoceptor stimulation by isoprenaline and methoxamine on the contractile force and cAMP level of the isolated rabbit papillary muscle. Naunyn Schmiedebergs Arch Pharmacol. 1975;289(3):291–302. doi: 10.1007/BF00499982. [DOI] [PubMed] [Google Scholar]
  27. Selwyn M. J., Dawson A. P., Dunnett S. J. Calcium transport in mitochondria. FEBS Lett. 1970 Sep 18;10(1):1–5. doi: 10.1016/0014-5793(70)80402-1. [DOI] [PubMed] [Google Scholar]
  28. Sluse F. E., Sluse-Goffart C. M., Duyckaerts C., Liébecq C. Evidence for cooperative effects in the exchange reaction catalysed by the oxoglutarate translocator of rat-heart mitochondria. Eur J Biochem. 1975 Aug 1;56(1):1–14. doi: 10.1111/j.1432-1033.1975.tb02201.x. [DOI] [PubMed] [Google Scholar]
  29. Taylor W. M., Prpić V., Exton J. H., Bygrave F. L. Stable changes to calcium fluxes in mitochondria isolated from rat livers perfused with alpha-adrenergic agonists and with glucagon. Biochem J. 1980 May 15;188(2):443–450. doi: 10.1042/bj1880443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. WILLIAMSON J. R. METABOLIC EFFECTS OF EPINEPHRINE IN THE ISOLATED, PERFUSED RAT HEART. I. DISSOCIATION OF THE GLYCOGENOLYTIC FROM THE METABOLIC STIMULATORY EFFECT. J Biol Chem. 1964 Sep;239:2721–2729. [PubMed] [Google Scholar]
  31. Williamson J. R. Metabolic effects of epinephrine in the perfused rat heart. II. Control steps of glucose and glycogen metabolism. Mol Pharmacol. 1966 May;2(3):206–220. [PubMed] [Google Scholar]
  32. Yamada E. W., Shiffman F. H., Huzel N. J. Ca2+-regulated release of an ATPase inhibitor protein from submitochondrial particles derived from skeletal muscles of the rat. J Biol Chem. 1980 Jan 10;255(1):267–273. [PubMed] [Google Scholar]

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