Structural, Biochemical, and Elemental Correlates of Injury in Cultured Cardiac Cells

  • Ann Lefurgey
  • Elizabeth Murphy
  • Bernhard Wagenknecht
  • Peter Ingram
  • Melvyn Lieberman
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Several investigators (Trumpet al., 1976; Nayler, 1981; Nayler and Grinwald, 1981; J. G. Murphyet al., 1987) have suggested that the movement and redistribution of cellular ion contents, especially calcium, play a key role in the pathophysiology of cardiac ischemia. Since 1982 (Murphyet al.) our investigations have focused on the study of subcellular ionic mechanisms underlying this pathophysiology. We have utilized a model system of heart cells grown in culture to obtain basic information about (1) the regulation of ion transport in cardiac cells (Liebermanet al., 1984) and (2) the relationship between maintenance of ionic homeostasis, metabolic integrity, and the onset of irreversible cell injury (Liebermanet al., 1985).


Cell Injury Transmission Electron Micrographs Metabolic Inhibition Heart Cell Iodoacetic Acid 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Broderick, R., Wasserman, A. J., Fujimori, T., and Somlyo, A. P., 1986, Mitochondrial Ca2+ uptake during massive cellular Na+ efflux and its reversibility in situ: An electron probe study, J. Gen. Physiol. 88:13a.Google Scholar
  2. Buja, L. M., Hagler, H. K., Parsons, D., Chien, K., Reynolds, R. C., and Willerson, J. T., 1985, Alterations of ultrastructure and elemental composition in cultured neonatal rat cardiac myocytes after metabolic inhibition with iodoacetic acid, Lab. Invest. 53:397–412.PubMedGoogle Scholar
  3. Chien, K. R., Sen, A., Reynolds, R., Chang, A., Kim, Y., Gunn, M. D., Buja, L. M., and Willerson, J. T., 1985, Release of arachidonate from membrane phospholipids in cultured neonatal rat myo-cardial cells during ATP depletion. Correlation with the progression of cell injury, J. Clin. Invest. 75:1770–1780.PubMedCrossRefGoogle Scholar
  4. Doorey, A. J., and Barry, W. H., 1983, The effects of inhibition of oxidative phosphorylation and glycolysis on contractility and high energy phosphate content in cultured chick heart cells, Circ. Res. 53:192–201.PubMedGoogle Scholar
  5. Ebihara, L., Shigeto, N., Lieberman, M., and Johnson, E. A., 1980, The initial inward current in spherical clusters of chick embryonic heart cells, J. Gen. Physiol. 75:437–456.PubMedCrossRefGoogle Scholar
  6. Gunn, M. D., Sen, A., Chang, A., Willerson, J. T., Buja, L. M., and Chien, K. R., 1985, Mechanisms of accumulation of arachidonic acid in cultured myocardial cells during ATP depletion, Am. J. Physiol. 249:(Heart Circ. Physiol. 18) H1188–H1194.PubMedGoogle Scholar
  7. Hall, T. A., 1979, Biological x-ray microanalysis, J. Microsc. 117:145–163.PubMedCrossRefGoogle Scholar
  8. Hasin, Y., and Barry, W. H., 1984, Myocardial metabolic inhibition and membrane potential, contraction, and potassium uptake, Am. J. Physiol. 247:(Heart Circ. Physiol. 16):H322–H329.PubMedGoogle Scholar
  9. Jennings, R. B., and Reimer, K. A., 1981, Lethal myocardial ischemic injury, Am. J. Pathol. 102: 241–255.PubMedGoogle Scholar
  10. Kane, A. B., Petrovich, D. R., Stern, R. O., and Farber, J. L., 1985, ATP depletion and loss of cell integrity in anoxic hepatocytes and silica-treated P388D macrophages, Am. J. Physiol. 249 (Cell Physiol. 18):C256–C266.PubMedGoogle Scholar
  11. Kishimoto, A., Kajikawa, N., Shiota, M., and Nioshizuka, Y., 1983, Proteolytic activation of calciumactivated, phospholipid-dependent kinase by calcium dependent neutral protease, J. Biol. Chem. 258:1156–1164.PubMedGoogle Scholar
  12. Kitazawa, T., Shuman, H., and Somlyo, A. P., 1983, Quantitative electron probe analysis: Problems and solutions, Ultramicroscopy 11:251–262.CrossRefGoogle Scholar
  13. LeFurgey, A., Hawkey, L. A., Lieberman, M., and Ingram, P., 1987, Na-Ca compartmentation in cultured heart cells, Microbeam Analysis 1987:267–268.Google Scholar
  14. LeFurgey, A., Liu, S., Lieberman, M., and Ingram, P., 1986, Quantitative elemental characterization of cultured heart cells by electron probe x-ray microanalysis and ion selective electrodes, Microbeam Analysis 1986:205–208.Google Scholar
  15. Lieberman, M., Horres, C. R., Jacob, R., Murphy, E., Piwnica-Worms, D., and Wheeler, D. M., 1984, Physiologic criteria for electrogenic transport in tissue-cultured heart cells, in: Electrogenic Transport: Fundamental Principles and Physiological Implications (M. P. Blaustein and M. Lieberman, eds.), Raven Press, New York, pp. 181–191.Google Scholar
  16. Lieberman, M., LeFurgey, A., Murphy, E., and Liu, S., 1985, Cultured heart cells as a model for studying myocardial ischemia, in: Pathology of Cardiovascular Injury (H. S. Stone and W. B. Weglicki, eds.), Martinus Nijhoff, Boston, pp. 145–155.CrossRefGoogle Scholar
  17. Murphy, E., Aiton, J. F., Horres, C. R., and Lieberman, M., 1983, Calcium elevation in cultured heart cells: Its role in cell injury, Am. J. Physiol. 24S:(Cell Physiology 14)C316–C321.Google Scholar
  18. Murphy, E., LeFurgey, A., and Lieberman, M., 1987, Biochemical and structural changes in cultured heart cells induced by metabolic inhibition, Am. J. Physiol. 253:(Cell Physiology 22)C700–C706.PubMedGoogle Scholar
  19. Murphy, E., LeFurgey, A., Horres, C. R., and Lieberman, M., 1982, Hypoxia and calcium in cultured heart cell injury, Fed. Proc. 41:1273 (abstr.).Google Scholar
  20. Murphy, E., Jacob, R., and Lieberman, M., 1985, Cytosolic free calcium in chick heart cells: Its role in cell injury, J. Mol. Cell. Cardiol. 17:221–231.PubMedCrossRefGoogle Scholar
  21. Murphy, E., Wheeler, D. M., LeFurgey, A., Jacob, R., Lobaugh, L. A., and Lieberman, M., 1986, Coupled sodium-calcium transport in cultured chick heart cells, Am. J. Physiol. 250 (Cell Physiol. 19):C442–C452.PubMedGoogle Scholar
  22. Murphy, J. G., Marsh, J. D., and Smith, T. W., 1987, The role of calcium in ischemic injury, Circulation 75 (suppl. V):V15–V24.PubMedGoogle Scholar
  23. Nayler, W. G., and Grinwald, P., 1981, Calcium entry blockers and myocardial function, Fed. Proc. 40:2855–2861.PubMedGoogle Scholar
  24. Nayler, W. G., 1981, The role of calcium in the ischemic myocardium, Am. J. Pathol. 102:262–270.PubMedGoogle Scholar
  25. Neely, J. R., and Grotyohann, L. W., 1984, Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts. Circ. Res. 55:816–824.PubMedGoogle Scholar
  26. Shuman, H., Somlyo, A. V., and Somlyo, A. P., 1976, Quantitative electron probe microanalysis of biological thin sections: Methods and validity, Ultramicroscopy 1:317–339.PubMedCrossRefGoogle Scholar
  27. Trump, B. F., Mergner, W. J., Kahng, M. W., and Saladino, A. J., 1976, Studies on the subcellular pathophysiology of ischemia, Circulation 53:Suppl. 117–126.Google Scholar
  28. Wagenknecht, B., LeFurgey, A., and Lieberman, M., 1987, Response of cultured embryonic chick heart cells to hypoxia, Fed. Proc. 46(3):529.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Ann Lefurgey
    • 1
  • Elizabeth Murphy
    • 2
  • Bernhard Wagenknecht
    • 1
  • Peter Ingram
    • 3
  • Melvyn Lieberman
    • 1
  1. 1.Department of PhysiologyDuke University Medical CenterDurhamUSA
  2. 2.Laboratory of Molecular BiophysicsNational Institute of Environmental Health SciencesResearch Triangle ParkUSA
  3. 3.Research Triangle InstituteResearch Triangle ParkUSA

Personalised recommendations