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. 1983 Jun;339:107–122. doi: 10.1113/jphysiol.1983.sp014706

Intracellular calcium concentration during hypoxia and metabolic inhibition in mammalian ventricular muscle.

D G Allen, C H Orchard
PMCID: PMC1199151  PMID: 6887018

Abstract

Papillary muscles from rats, cats and ferrets were microinjected with aequorin, a photoprotein which emits light as a function of Ca2+ concentration. The effects of hypoxia and different types of metabolic inhibition on intracellular Ca2+ concentration ([ Ca2+]i) and tension were studied. 2. Exposure of the muscle to hypoxia (PO2 less than 5 mmHg) or CN- caused a reversible decrease in developed tension, with no change in the magnitude of the Ca transient associated with each contraction. The rate of decline of the Ca transient was decreased slightly but significantly during these interventions. 3. In half the preparations examined, the initial fall in tension produced by hypoxia was interrupted by a short-lived increase in developed tension. No change in the Ca transient was associated with this increase in tension. 4. After exposure of papillary muscles to glucose-free Tyrode solution for short periods (less than 1 hr), hypoxia and CN- had a similar effect on the magnitude of the light transient and developed tension to section 2 above. After perfusion with glucose-free Tyrode solution for longer periods (greater than 2 hr), hypoxia and CN- caused a greater decrease in developed tension and a marked decrease in the magnitude of the Ca transient. 5. The addition of CN- to papillary muscles which were superfused with Tyrode solution containing 2-deoxyglucose instead of glucose, caused a rapid decrease in the magnitude of the Ca transient and of developed tension. These changes were not fully reversible. 6. In muscles which developed an hypoxic contracture, the resting [Ca2+]i did not rise by more than a factor of 1.4. 7. It is concluded that when glycolysis can proceed, inhibition of oxidative phosphorylation results in a decrease in developed tension with no change in the magnitude of the Ca transient. This decrease in the apparent sensitivity of the contractile proteins to Ca2+ is attributable to the decrease in intracellular pH known to occur in this situation. There may also be a second mechanism tending to reduce the Ca transient under these conditions. 8. During inhibition of glycolysis and oxidative phosphorylation, developed tension falls as a result of decreased Ca transients. This could be because the free energy of hydrolysis of ATP falls below the level required to pump Ca from the myoplasm to the sarcoplasmic reticulum.

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Selected References

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  1. Allen D. G., Kurihara S. Calcium transients in mammalian ventricular muscle. Eur Heart J. 1980;Suppl A:5–15. doi: 10.1093/eurheartj/1.suppl_1.5. [DOI] [PubMed] [Google Scholar]
  2. Allen D. G., Orchard C. H. The effects of changes of pH on intracellular calcium transients in mammalian cardiac muscle. J Physiol. 1983 Feb;335:555–567. doi: 10.1113/jphysiol.1983.sp014550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bailey I. A., Williams S. R., Radda G. K., Gadian D. G. Activity of phosphorylase in total global ischaemia in the rat heart. A phosphorus-31 nuclear-magnetic-resonance study. Biochem J. 1981 Apr 15;196(1):171–178. doi: 10.1042/bj1960171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blinks J. R., Prendergast F. G., Allen D. G. Photoproteins as biological calcium indicators. Pharmacol Rev. 1976 Mar;28(1):1–93. [PubMed] [Google Scholar]
  5. Curtin N. A., Woledge R. C. Energy changes and muscular contraction. Physiol Rev. 1978 Jul;58(3):690–761. doi: 10.1152/physrev.1978.58.3.690. [DOI] [PubMed] [Google Scholar]
  6. Dawson M. J., Gadian D. G., Wilkie D. R. Mechanical relaxation rate and metabolism studied in fatiguing muscle by phosphorus nuclear magnetic resonance. J Physiol. 1980 Feb;299:465–484. doi: 10.1113/jphysiol.1980.sp013137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ellis D., Thomas R. C. Direct measurement of the intracellular pH of mammalian cardiac muscle. J Physiol. 1976 Nov;262(3):755–771. doi: 10.1113/jphysiol.1976.sp011619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Endo M. Calcium release from the sarcoplasmic reticulum. Physiol Rev. 1977 Jan;57(1):71–108. doi: 10.1152/physrev.1977.57.1.71. [DOI] [PubMed] [Google Scholar]
  9. Fabiato A., Fabiato F. Effects of magnesium on contractile activation of skinned cardiac cells. J Physiol. 1975 Aug;249(3):497–517. doi: 10.1113/jphysiol.1975.sp011027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fabiato A., Fabiato F. Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiace and skeletal muscles. J Physiol. 1978 Mar;276:233–255. doi: 10.1113/jphysiol.1978.sp012231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Garlick P. B., Radda G. K., Seeley P. J. Studies of acidosis in the ischaemic heart by phosphorus nuclear magnetic resonance. Biochem J. 1979 Dec 15;184(3):547–554. doi: 10.1042/bj1840547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gibbs C. L. Cardiac energetics. Physiol Rev. 1978 Jan;58(1):174–254. doi: 10.1152/physrev.1978.58.1.174. [DOI] [PubMed] [Google Scholar]
  13. Gudbjarnason S., Mathes P., Ravens K. G. Functional compartmentation of ATP and creatine phosphate in heart muscle. J Mol Cell Cardiol. 1970 Sep;1(3):325–339. doi: 10.1016/0022-2828(70)90009-x. [DOI] [PubMed] [Google Scholar]
  14. Hearse D. J., Chain E. B. The role of glucose in the survival and 'recovery' of the anoxic isolated perfused rat heart. Biochem J. 1972 Aug;128(5):1125–1133. doi: 10.1042/bj1281125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hearse D. J. Oxygen deprivation and early myocardial contractile failure: a reassessment of the possible role of adenosine triphosphate. Am J Cardiol. 1979 Nov;44(6):1115–1121. doi: 10.1016/0002-9149(79)90177-2. [DOI] [PubMed] [Google Scholar]
  16. KIPNIS D. M., CORI C. F. Studies of tissue permeability. V. The penetration and phosphorylation of 2-deoxyglucose in the rat diaphragm. J Biol Chem. 1959 Jan;234(1):171–177. [PubMed] [Google Scholar]
  17. Kammermeier H., Schmidt P., Jüngling E. Free energy change of ATP-hydrolysis: a causal factor of early hypoxic failure of the myocardium? J Mol Cell Cardiol. 1982 May;14(5):267–277. doi: 10.1016/0022-2828(82)90205-x. [DOI] [PubMed] [Google Scholar]
  18. Katz A. M., Hecht H. H. Editorial: the early "pump" failure of the ischemic heart. Am J Med. 1969 Oct;47(4):497–502. doi: 10.1016/0002-9343(69)90180-6. [DOI] [PubMed] [Google Scholar]
  19. Kübler W., Katz A. M. Mechanism of early "pump" failure of the ischemic heart: possible role of adenosine triphosphate depletion and inorganic phosphate accumulation. Am J Cardiol. 1977 Sep;40(3):467–471. doi: 10.1016/0002-9149(77)90174-6. [DOI] [PubMed] [Google Scholar]
  20. Kübler W., Spieckermann P. G. Regulation of glycolysis in the ischemic and the anoxic myocardium. J Mol Cell Cardiol. 1970 Dec;1(4):351–377. doi: 10.1016/0022-2828(70)90034-9. [DOI] [PubMed] [Google Scholar]
  21. Lewis M. J., Housmans P. R., Claes V. A., Brutsaert D. L., Henderson A. H. Myocardial stiffness during hypoxic and reoxygenation contracture. Cardiovasc Res. 1980 Jun;14(6):339–344. doi: 10.1093/cvr/14.6.339. [DOI] [PubMed] [Google Scholar]
  22. McDonald T. F., MacLeod D. P. Metabolism and the electrical activity of anoxic ventricular muscle. J Physiol. 1973 Mar;229(3):559–582. doi: 10.1113/jphysiol.1973.sp010154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nayler W. G., Poole-Wilson P. A., Williams A. Hypoxia and calcium. J Mol Cell Cardiol. 1979 Jul;11(7):683–706. doi: 10.1016/0022-2828(79)90381-x. [DOI] [PubMed] [Google Scholar]
  24. Nayler W. G., Yepez C. E., Poole-Wilson P. A. The effect of beta-adrenoceptor and Ca2+ antagonist drugs on the hypoxia-induced increased in resting tension. Cardiovasc Res. 1978 Nov;12(11):666–674. doi: 10.1093/cvr/12.11.666. [DOI] [PubMed] [Google Scholar]
  25. Neely J. R., Bowman R. H., Morgan H. E. Effects of ventricular pressure development and palmitate on glucose transport. Am J Physiol. 1969 Apr;216(4):804–811. doi: 10.1152/ajplegacy.1969.216.4.804. [DOI] [PubMed] [Google Scholar]
  26. SHIMOMURA O., JOHNSON F. H., SAIGA Y. Extraction, purification and properties of aequorin, a bioluminescent protein from the luminous hydromedusan, Aequorea. J Cell Comp Physiol. 1962 Jun;59:223–239. doi: 10.1002/jcp.1030590302. [DOI] [PubMed] [Google Scholar]
  27. Somlyo A. V., Gonzalez-Serratos H. G., Shuman H., McClellan G., Somlyo A. P. Calcium release and ionic changes in the sarcoplasmic reticulum of tetanized muscle: an electron-probe study. J Cell Biol. 1981 Sep;90(3):577–594. doi: 10.1083/jcb.90.3.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wilkie D. R. Generation of protons by metabolic processes other than glycolysis in muscle cells: a critical view. J Mol Cell Cardiol. 1979 Mar;11(3):325–330. doi: 10.1016/0022-2828(79)90446-2. [DOI] [PubMed] [Google Scholar]

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