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Intracellular calcium regulatory systems during ischemia and reperfusion

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Myocardial Ischemia: Mechanisms, Reperfusion, Protection

Part of the book series: EXS ((EXS,volume 76))

Abstract

Mitochondrial oxidative phosphorylation provides most of the ATP needed for excitation—contraction coupling and other energy-dependent reactions in cardiac muscle. Mitochondria also accumulate and release Ca2+ but are thought not to influence cytosolic free [Ca2+] ([Ca2+]i) to an appreciable extent except under pathologic conditions. [Ca2+]i is regulated primarily by Ca2+ flux across the sarcolemma and by Ca2+ uptake and release by the sarcoplasmic reticulum (SR). Calcium-induced SR Ca2+ release initiates cardiac muscle contraction while Ca2+ reaccumulation by the SR leads to relaxation.

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References

  1. Baysal K, Jung DW, Gunter KK, Gunter TE, Brierley GP. Na+-dependent Ca2+ efflux mechanism of heart mitochondria is not a passive Ca2+/2Na+ exchanger. Am J Physiol Cell Physiol 1994; 266: C800 – C808.

    CAS  Google Scholar 

  2. Gunter TE, Pfeiffer DR. Mechanisms by which mitochondria transport calcium. Am J Physiol 1990; 258: C755 – C786.

    PubMed  CAS  Google Scholar 

  3. Gunter TE, Gunter KK, Sheu S-S, Gavin CE. Mitochondrial calcium transport: physiological and pathological relevance. Am J Physiol 1994; 267: C313 – C339

    PubMed  CAS  Google Scholar 

  4. Di Lisa F, Gambassi G, Spurgeon H, Hansford RG. Intramitochondrial free calcium in cardiac myocytes in relation to dehydrogenase activation. Cardiovasc Res 1993; 27: 1840 – 1844.

    Article  Google Scholar 

  5. Miyata H, Silverman HS, Sollott SJ, Lakatta EG, Stern MD, Hansford RG. Measurement of mitochondrial free Ca2+ concentration in living single rat cardiac myocytes. Am J Physiol Heart Circ Physiol 1991; 261: H1123 – H1134.

    CAS  Google Scholar 

  6. Ying W-L, Emerson J, Clarke MJ, Sanadi DR. Inhibition of mitochondrial calcium ion transport by an oxo-bridged dinuclear ruthenium ammine complex. Biochemistry 1991; 30: 4949 – 4952.

    Article  PubMed  CAS  Google Scholar 

  7. Haworth RA, Hunter DR. The Ca2+-induced membrane transition in mitochondria. II Nature of the Ca2+ trigger site. Arch Biochem Biophys 1979; 195: 460 – 467.

    Article  PubMed  CAS  Google Scholar 

  8. Hunter DR, Haworth RA. The Ca2+-induced membrane transition in mitochondria. Ill Transitional Ca2+ release. Arch Biochem Biophys 1979; 195: 468 – 477.

    Article  PubMed  CAS  Google Scholar 

  9. Hunter DR, Haworth RA. The Ca2+-induced membrane transition in mitochondria. I. The protective mechanisms. Arch Biochem Biophys 1979; 195: 453 – 459.

    Article  PubMed  CAS  Google Scholar 

  10. Haworth RA, Hunter DR. Allosteric inhibition of the Ca2+-activated hydrophilic channel of the mitochondrial inner membrane by nucleotides. J Membr Biol 1980; 54: 231 – 236.

    Article  PubMed  CAS  Google Scholar 

  11. Hunter Dr, Haworth RA, Southard JH. Relationship between configuration, function, and permeability in calcium-treated mitochondria. J. Biol Chem 1976; 251: 5069 – 5077.

    PubMed  CAS  Google Scholar 

  12. Fournier N, Ducet G, Crevat A. Action of cyclosporine on mitochondrial calcium fluxes. J Bioenerg Biomembr 1987; 19: 297 – 303.

    Article  PubMed  CAS  Google Scholar 

  13. Broekemeier KM, Dempsey ME, Pfeiffer DR. Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria. J Biol Chem 1989; 264: 7826 – 7830.

    PubMed  CAS  Google Scholar 

  14. Crompton M, Ellinger H, Costi A. Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress. Biochem J 1988; 255: 357 – 360.

    PubMed  CAS  Google Scholar 

  15. Szabo I, Zoratti M. The mitochondrial megachannel is the permeability transition pore. J Bioenerg Biomembr 1992; 24: 111 – 117.

    Article  PubMed  CAS  Google Scholar 

  16. Broekemeier KM, Carpenter-Deyo L, Reed DJ, Pfeiffer DR: Cyclosporine A protects hepatocytes subjected to high Ca2+ and oxidative stress. FEBS Lett 1992; 304: 1992 – 194.

    Google Scholar 

  17. Pastorino JG, Snyder JW, Serroni A, Hoek JB, Farber JL. Cyclosporin and carnitine prevent the anoxic death of cultured hepatocytes by inhibiting the mitochondrial permeability transition. J Biol Chem 1993; 268: 13791 – 13798.

    PubMed  CAS  Google Scholar 

  18. Imberti R, Nieminen AL, Herman B, Lemasters JJ. Mitochondrial and glycolytic dysfunction in lethal injury to hepatocytes by T-butylhydroperoxide: protection by fructose, cyclosporin A and trifluoperazine. J Pharmacol Exp Ther 1993; 265: 392 – 400.

    PubMed  CAS  Google Scholar 

  19. Kass GEN, Juedes MJ, Orrenius S. Cyclosporin A protects hepatocytes against prooxidant-induced cell killing. A study on the role of mitochondrial Ca2+ cycling in cytotoxicity. Biochem Pharmacol 1992; 44: 1995 – 2003.

    Article  PubMed  CAS  Google Scholar 

  20. Crompton M, Costi A. A heart mitochondrial Ca2+-dependent port of possible relevance to reperfusion-induced injury. Evidence that ADP facilitates pore interconversion between the closed and open states. Biochem J 1990; 266: 33 – 39.

    PubMed  CAS  Google Scholar 

  21. Crompton M, Costi A. Kinetic evidence for a heart mitochondrial port activated by Ca2+, inorganic phosphate and oxidative stress. A potential mechanism for mitochondrial dysfunction during cellular Ca2+ overload. Eur J Biochem 1988; 178: 489 – 501.

    Article  PubMed  CAS  Google Scholar 

  22. Crompton M, Costi A, Hayat L. Evidence for the presence of a reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria. Biochem J 1987; 245: 915 – 918.

    PubMed  CAS  Google Scholar 

  23. Nazareth W, Yafei N, Crompton M. Inhibition of anoxia-induced injury in heart myocytes by cyclosporin A. J Mol Cell Cardiol 1991; 23: 1351 – 1354.

    Article  PubMed  CAS  Google Scholar 

  24. Duchen MR, McGuinness O, Broon LA, Crompton M. On the involvement of a cyclosporin A sensitive mitochondrial pore in myocardial reperfusion injury. Cardiovasc Res 1993; 27: 1790 – 1794.

    Article  PubMed  CAS  Google Scholar 

  25. Crompton M, Andreeva L. On the involvement of a mitochondrial pore in reperfusion injury. Basic Res Cardiol 1993; 88: 513 – 523.

    Article  PubMed  CAS  Google Scholar 

  26. Griffiths EJ, Halestrap AP. Protection by cyclosporin A of ischemia/reperfusion-induced damage in isolated rat hearts. J Mol Cell Cardiol 1993; 25: 1461 – 1469.

    Article  PubMed  CAS  Google Scholar 

  27. Gabel S, Steenbergen C, London R, Murphy E. The effects of cyclosporin A on ischemic injury in perfused rat heart. J Mol Cell Cardiol 1994; 26: CLXXII (Abstract).

    Google Scholar 

  28. Banijamali HS, Ter Keurs MHC, Paul LC, Ter Keurs HEDJ. Excitation-contraction coupling in rat heart: influence of cyclosporin A. Cardiovasc Res 1993; 27: 1845 – 1854.

    Article  PubMed  CAS  Google Scholar 

  29. Moia LJMP, Matsui H, De Barros GAM, Tomizawa K, Miyamoto K, Kuwata Y, Tokuda M, Itano T, Hatase O. Immunosuppressants and calcineurin inhibitors, cyclosporin A and FK506, reversibly inhibit epileptogenesis in amygdaloid kindled rat. Brain Res 1994; 648: 337 – 341.

    Article  PubMed  CAS  Google Scholar 

  30. Ryffel B, Woerly G, Murray M, Eugster HP, Car B. Binding of active cyclosporins to cyclophilin A and B, complex formation with calcineurin A. Biochem Biophys Res Commun 1993; 194: 1074 – 1083.

    Article  PubMed  CAS  Google Scholar 

  31. Breuder T, Hemenway CS, Movva NR, Cardenas ME, Heitman J. Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains. Proc Natl Acad Sci USA 1994; 91: 5372 – 5376.

    Article  PubMed  CAS  Google Scholar 

  32. Bernardi P, Broekmeier KM, Pfeiffer DR. Recent progress on regulation of the mitochondrial permeability transition pore; a cyclosporin sensitive pore in the inner mitochondrial membrane. J Bioenerg Biomemb 1994; 26: 509 – 517.

    Article  CAS  Google Scholar 

  33. Timerman AP, Altschuld RA, Hohl CM, Brierley GP, Merola AJ. Cellular glutathione and the response of adult rat heart myocytes to oxidant stress. J Mol Cell Cardiol 1990; 22: 565 – 575.

    Article  PubMed  CAS  Google Scholar 

  34. Altschuld RA, Wenger WC, Lamka KG, Kindig OR, Capen CC, Mizuhira V, Vander Heide RS, Brierley GP. Structural and functional properties of adult rat heart myocytes lysed with digitonin. J Biol Chem 1985; 260: 14325 – 14334.

    PubMed  CAS  Google Scholar 

  35. Bernardi P. Modulation of the mitochondrial cyclosporin A-sensitive permeability transition pore by the proton electrochemical gradient. Evidence that the pore can be opened by membrane depolarization. J Biol Chem 1992; 267: 8834 – 8839.

    PubMed  CAS  Google Scholar 

  36. Rouslin W, Broge CW. Mechanisms of ATP conservation during ischemia in slow and fast heart rate hearts. Am J Physiol Cell Physiol 1993; 264: C209 – C216.

    CAS  Google Scholar 

  37. Rouslin W, Broge CW. Regulation of mitochondrial matrix pH and adenosine 5’-triphosphatase activity during ischemia in slow heart-rate hearts: role of Pi/H+ symport. J Biol Chem 1989; 264: 15224 – 15229.

    PubMed  CAS  Google Scholar 

  38. Nocolli A, Petronilli V, Bernardi P. Modulation of the mitochondrial cyclosporin A-sensitive permeability transition pore by matrix pH. Evidence that the pore open-closed probability is regulated by reversible fastidine protonation. Biochemistry 1993; 32: 4461 – 4465.

    Article  Google Scholar 

  39. Sako EY, Kingsley-Hickman PB, From AH, Foker JE, Ugurbil K. ATP synthesis kinetics and mitochondrial function in the postischemic myocardium as studied by 31P NMR. J Biol Chem 1988; 263: 10600 – 10607.

    PubMed  CAS  Google Scholar 

  40. Grover GJ, Dzwonczyk S, Sleph PG. Ruthenium red improves postischemic contractile function in isolated rat hearts. J Cardiovasc Pharmacol 1990; 16: 783 – 789.

    Article  PubMed  CAS  Google Scholar 

  41. Altschuld RA, Merola AJ, Brierley GP. The permeability of heart mitochondria to creatine. J Mol Cell Cardiol 1975; 7: 451 – 462.

    Article  PubMed  CAS  Google Scholar 

  42. Rauch U, Schulze K, Witzenbichler B, Schultheiß HP. Alteration of the cytosolic mitochondrial distribution of high-energy phosphates during global myocardial ischemia may contribute to early contractile failure. Cir Res 1994; 75: 760 – 769.

    CAS  Google Scholar 

  43. Soboll S, Conrad A, Hebisch S. Influence of mitochondrial creatine kinase on the mitochondrial/extramitochondrial distribution of high energy phosphates in muscle tissue: evidence for a leak in the creatine shuttle. Mol Cell Biochem 1994; 133 /134: 105 – 113.

    Article  PubMed  Google Scholar 

  44. Imai K, Wang T, Millard RW, Ashraf M, Kranias EG, Asano G, Grassi de Gende AO, Nagao T, Solaro RJ, Schwartz A. Ischaemia-induced changes in canine cardiac sarcoplasmic reticulum. Cardiovasc Res 1983; 17: 696 - 709.

    Article  PubMed  CAS  Google Scholar 

  45. Feher JJ, LeBolt WR, Manson NH. Differential effect of global ischemia on the ryanodine-sensitive and ryanodine-insensitive calcium uptake of cardiac sarcoplasmic reticulum. Circ Res 1989; 65: 1400 – 1408.

    PubMed  CAS  Google Scholar 

  46. Rapundalo ST, Briggs FN, Feher JJ. Effects of ischemia on the isolation and function of canine cardiac sarcoplasmic reticulum. J Mol Cell Cardiol 1986; 18: 837 – 851.

    Article  PubMed  CAS  Google Scholar 

  47. Feher J J, Briggs FN, Hess ML. Characterization of cardiac sarcoplasmic reticulum from ischemic myocardium: comparison of isolated sarcoplasmic reticulum with unfractionated homogenates. J Mol Cell Cardiol 1980; 12: 427 – 432.

    Article  PubMed  CAS  Google Scholar 

  48. Rehr RB, Fuhs BE, Hirsch JI, Feher JJ. Effect of brief regional ischemia followed by reperfusion with or without superoxide dismutase and catalase administration on myocardial sarcoplasmic reticulum and contractile function. Am Heart J 1991; 122: 1257 – 1269.

    Article  PubMed  CAS  Google Scholar 

  49. Lamers JM, Duncker DJ, Bezstarosti K, McFalls EO, Sassen LM A, Verdouw PD. Increased activity of the sarcoplasmic reticular calcium pump in porcine stunned myocardium. Cardiovasc Res 1993; 27: 520 – 524.

    Article  PubMed  CAS  Google Scholar 

  50. Kusuoka H, Porterfield JK, Weisman HF, Weisfeldt ML, Marban E. Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts. J Clin Invest 1987; 79: 950 – 961.

    Article  PubMed  CAS  Google Scholar 

  51. Marban E, Kitakaze M, Kusuoka H, Porterfield JK, Yu DT, Chacko VP. Intracellular free calcium concentration measured with 19F NMR spectroscopy in intact ferret hearts. Proc Natl Acad Sci USA 1987; 84: 6005 – 6009.

    Article  PubMed  CAS  Google Scholar 

  52. Meissner A, Morgan JP. Contractile dysfunction and abnormal Ca2+ modulation during postischemic reperfusion in rat heart. Am J Physiol Heart Circ Physiol 1995; 268: H100 – H111.

    CAS  Google Scholar 

  53. Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol 1983; 245: C1 – 14.

    PubMed  CAS  Google Scholar 

  54. Sipido KB, Wier WG. Flux of Ca2+ across the sarcoplasmic reticulum of guinea-pig cardiac cells during excitation-contraction coupling. J Physiol 1991; 435: 605 – 630.

    PubMed  CAS  Google Scholar 

  55. Wimsatt DK, Hohl CM, Brierley GP, Altschuld RA. Calcium accumulation and release by the sarcoplasmic reticulum of digitonin-lysed adult mammalian ventricular cardiomyocytes. J Biol Chem 1990; 265: 14849 – 14857.

    PubMed  CAS  Google Scholar 

  56. Davis MD, Lebolt W, Feher JJ. Reversibility of the effects of normothermic global ischemia on the ryanodine-sensitive and ryanodine-insensitive calcium uptake of cardiac sarcoplasmic reticulum. Circ Res 1992; 70: 163 – 171.

    PubMed  CAS  Google Scholar 

  57. Feher JJ, Alderson BH, Lipford GB. The role of passive efflux pathways in determining steady-state loading in canine cardiac sarcoplasmic reticulum vesicles. Prog Clin Biol Res 1988; 252: 149 – 154.

    PubMed  CAS  Google Scholar 

  58. Feher JJ, Manson NH, Poland JL. The rate and capacity of calcium uptake by sarcoplasmic reticulum in fast, slow, and cardiac muscle: effects of ryanodine and ruthenium red. Arch Biochem Biophys 1988; 265: 171 – 182.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Biochemistry, The Ohio State University Medical Center, 43210-1218, Columbus, OH, USA

    R. A. Altschuld

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  1. R. A. Altschuld
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Editors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Western Ontario, Medical Sciences Building, N6A 5C1, London, Ontario, Canada

    Morris Karmazyn PhD (Professor and Career Investigator of the Heart and Stroke Foundation of Ontario) (Professor and Career Investigator of the Heart and Stroke Foundation of Ontario)

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© 1996 Birkhäuser Verlag Basel/Switzerland

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Altschuld, R.A. (1996). Intracellular calcium regulatory systems during ischemia and reperfusion. In: Karmazyn, M. (eds) Myocardial Ischemia: Mechanisms, Reperfusion, Protection. EXS, vol 76. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-8988-9_6

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  • DOI: https://doi.org/10.1007/978-3-0348-8988-9_6

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-9857-7

  • Online ISBN: 978-3-0348-8988-9

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