Advertisement

Pathogenetic Roles of Intracellular Calcium and Magnesium in Membrane-Mediated Progressive Muscle Degeneration in Duchenne Muscular Dystrophy

  • Syamal K. Bhattacharya
  • Alice J. Crawford
  • Jay H. Thakar
  • Patti L. Johnson
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Duchenne muscular dystrophy (DMD) in humans is a progressively crippling X-linked recessive neuromuscular disease with no effective treatment (Rowland, 1980; Moser, 1984). It is characterized by profound biochemical (Kar and Pearson, 1976; Bertoriniet al., 1982; Bhattacharya and Crawford, 1985), electrocardiographic (Sanyal and Johnson, 1982), histopathological (Bodensteiner and Engel, 1978; Emery and Burt, 1980; Bertoriniet al., 1982, 1984), and ultrastructural (Mokri and Engel, 1975; Oberc and Engel, 1977) abnormalities of skeletal and cardiac muscle, and a 70–80% reduced life expectancy. Although a “vascular hypothesis” implicating abnormal microvasculature has been presented in the past to explain many aspects of the dystrophic pathophysiology, the most tenable mechanism for the classical muscle degeneration in DMD is now widely attributed to a generalized functional and structural defect(s) in the plasma membrane integrity of myofibers (Mokri and Engel, 1975; Schotlandet al., 1977) and erythroeytes (Araki and Mawatari, 1971).

Keywords

Muscular Dystrophy Duchenne Muscular Dystrophy Spinal Muscular Atrophy Duchenne Muscular Dystrophy Duchenne Muscular Dystrophy Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Araki, S., and Mawatari, S., 1971, Ouabain and erythrocyte-ghost adenosine triphosphatase. Effects in human muscular dystrophies, Arch. Neurol. 24:187–190.PubMedCrossRefGoogle Scholar
  2. Bertorini, T. E., Bhattacharya, S. K., Palmieri, G. M. A., Chesney, C. M., Pifer, D., and Baker, B., 1982, Muscle calcium and magnesium content in Duchenne muscular dystrophy, Neurology 32: 1088–1092.PubMedGoogle Scholar
  3. Bertorini, T. E., Cornelio, F., Bhattacharya, S. K., Palmieri, G. M. A., Dones, I., Dworzak, F., and Brambati, B., 1984, Calcium and magnesium content in fetuses at risk and prenecrotic Duchenne muscular dystrophy, Neurology 34:1436–1440.PubMedGoogle Scholar
  4. Bhattacharya, S. K., and Crawford, A. J., 1985, Preliminary evidence of magnesium depletion and excessive calcium accumulation in human myoblasts of dystrophic origin, Soc. Neurosci. Abstr. 11:1302.Google Scholar
  5. Bhattacharya, S. K., and Crawford, A. J., 1986, Beneficial effects of adenosine triphosphate-magnesium chloride administration in muscular dystrophy, Soc. Neurosci. Abstr. 12:264.Google Scholar
  6. Bhattacharya, S. K., Crawford, A. J., and Emery, A. E. H., 1984, Quantitation of total calcium in fetal muscle: A differential antenatal diagnosis for Duchenne muscular dystrophy, Clin. Res. 32: 288.Google Scholar
  7. Bhattacharya, S. K., Crawford, A. J., and Pate, J. W., 1987a, Electrocardiographic, biochemical, and morphologic abnormalities in dystrophic hamsters with cardiomyopathy, Muscle Nerve 10:168–176.PubMedCrossRefGoogle Scholar
  8. Bhattacharya, S. K., Lopez, J. R., Sanchez, V., Crawford, A. J., Vergara, J. L., and Sreter, F., 1987b, Direct evidence of membrane-mediated cellular degeneration by changes in the intracellular free calcium, potassium, and sodium concentrations in dystrophic hamsters, Soc. Neurosci. Abstr. 13: 1680.Google Scholar
  9. Bhattacharya, S. K., Palmieri, G. M. A., Bertorini, T. E., and Nutting, D. F., 1982, The effects of diltiazem in dystrophic hamsters, Muscle Nerve 5:73–78.PubMedCrossRefGoogle Scholar
  10. Bhattacharya, S. K., Williams, J. C., and Palmieri, G. M. A., 1979, Determination of calcium and magnesium in cardiac and skeletal muscle by atomic absorption spectroscopy using stoichiometric nitrous oxide-acetylene flame, Anal. Lett. 12:1451–1475.CrossRefGoogle Scholar
  11. Bodensteiner, J. B., and Engel, A. G., 1978, Intracellular calcium accumulation in Duchenne dystrophy and other myopathies: A study of 567,000 muscle fibers in 114 biopsies, Neurology 28:439–446.PubMedGoogle Scholar
  12. Brambati, B., Cornelio, F., Dworzak, F., and Dones, I., 1980, Calcium-positive muscle fibres in fetuses at risk for Duchenne muscular dystrophy, Lancet 2:969–970.PubMedCrossRefGoogle Scholar
  13. Carpenter, S., and Karpati, G., 1979, Duchenne muscular dystrophy: Plasma membrane loss initiates muscle cell necrosis unless it is repaired, Brain 102:147–161.PubMedCrossRefGoogle Scholar
  14. Chizzonite, R. A., and Zak, R., 1981, Calcium-induced cell death: Susceptibility of cardiac myocytes is age-dependent, Science 213:1508–1510.PubMedCrossRefGoogle Scholar
  15. Crawford, A. J., and Bhattacharya, S. K., 1987, Regulation of membrane-mediated chronic muscle degeneration by Diltiazem, Nifedipine and Verapamil in dystrophic hamsters, Soc. Neurosci. Abstr. 13:1680.Google Scholar
  16. Duncan, C. J., 1978, Role of intracellular calcium in promoting muscle damage: A strategy for controlling the dystrophic condition, Experientia 34:1531–1535.PubMedCrossRefGoogle Scholar
  17. Ebashi, S., and Sugita, H., 1979, The role of calcium in physiological and pathological processes of skeletal muscle, in: Current Topics in Nerve and Muscle Research ,ICS No. 455 (A. J. Aguayo and G. Karpati, eds.), Excerpta Medica, Amsterdam, pp. 73–84.Google Scholar
  18. Emery, A. E. H., and Burt, D., 1980, Intracellular calcium and pathogenesis and antenatal diagnosis of Duchenne muscular dystrophy, Br. Med. J. 280:355–357.PubMedCrossRefGoogle Scholar
  19. Emery, A. E. H., Skinner, R., Howden, L. C., and Matthews, M. B., 1982, Verapamil in Duchenne muscular dystrophy, Lancet 1:559.PubMedCrossRefGoogle Scholar
  20. Gustavii, B., Loefberg, L., and Enriksson, K. G., 1983, Fetal muscle biopsy, Acta Obstet. Gynecol. Scand. 62:369–371.PubMedCrossRefGoogle Scholar
  21. Kar, N. C., and Pearson, C. M., 1976, A calcium-activated neutral protease in normal and dystrophic human muscle, Clin. Chim. Acta 73:293–297.PubMedCrossRefGoogle Scholar
  22. Law, P. K., Luther, R. W., Goodwin, T. G., and Bhattacharya, S. K., 1983, Comparative mechano-physiologic studies on normal and dystrophic hamsters soleus muscles correlated with muscle calcium content, Clin. Res. 31:718.Google Scholar
  23. Maunder-Sewry, C. A., Gorodetsky, R., Yarom, R., and Dubowitz, V., 1980, Element analysis of skeletal muscle in Duchenne muscular dystrophy using X-ray fluorescence spectrometry, Muscle Nerve 3:502–508.PubMedCrossRefGoogle Scholar
  24. Mokri, B., and Engel, A. G., 1975, Duchenne dystrophy: Electron microscopic findings pointing to a basic or early abnormality in the plasma membrane of the muscle fiber, Neurology 25:1111–1120.PubMedGoogle Scholar
  25. Moser, H., 1984, Duchenne muscular dystrophy: Pathogenetic aspects and genetic prevention, Hum. Genet. 66:17–40.PubMedCrossRefGoogle Scholar
  26. Oberc, M. A., and Engel, W. K., 1977, Ultrastructural localization of calcium in normal and abnormal skeletal muscle, Lab. Invest. 36:566–577.PubMedGoogle Scholar
  27. Riedel, D. M., Entrikin, R. K., and Bhattacharya, S. K., 1988, Relevance of dystrophic chickens as an experimental model for hereditary muscular dystrophy in humans, Soc. Neurosci. Abstr. 14: 828.Google Scholar
  28. Rowland, L. P., 1980, Biochemistry of muscle membranes in Duchenne muscular dystrophy, Muscle Nerve 3:3–20.PubMedCrossRefGoogle Scholar
  29. Sanyal, S. K., and Johnson, W. W., 1982, Cardiac conduction abnormalities in children with Duchenne’s progressive muscular dystrophy: Electrocardiographic features and morphologic correlates, Cir culation 66:853–863.Google Scholar
  30. Schanne, F. A. X., Kane, A. B., Young, E. E., and Farber, J. L., 1979, Calcium dependence of toxic cell death: A final common pathway, Science 206:700–703.PubMedCrossRefGoogle Scholar
  31. Schotland, D. L., Bonilla, E., and Van Meter, M., 1977, Duchenne dystrophy: Alteration in muscle plasma membrane structure, Science 196:1005–1007.PubMedCrossRefGoogle Scholar
  32. Thakar, J. H., Wrogemann, K., and Balnehaer, M. C., 1973, Effect of ruthenium red on oxidative phosphorylation and the calcium and magnesium content of skeletal muscle mitochondria of normal and BIO 14.6 dystrophic hamsters, Biochim. Biophys. Acta 314:8–14.PubMedCrossRefGoogle Scholar
  33. Wrogemann, K., Blanchaer, M. C., Thakar, J. H., and Mezon, B. J., 1975, On the role of mitochondria in the hereditary cardiomyopathy of the Syrian hamster, in: Recent Advances in Studies on Cardiac Structure and Metabolism ,Vol. 6 (A. Fleckenstein and G. Rona, eds.), University Park Press, Baltimore, pp. 231–241.Google Scholar
  34. Wrogemann, K., and Pena, S. D. J., 1976, Mitochondrial calcium overload: A general mechanism for cell-necrosis in muscle diseases, Lancet 1:672–673.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Syamal K. Bhattacharya
    • 1
  • Alice J. Crawford
    • 1
  • Jay H. Thakar
    • 1
  • Patti L. Johnson
    • 1
  1. 1.Edward Dana Mitchell Surgical Research Laboratories, Departments of Surgery, Anatomy, and NeurobiologyUniversity of Tennessee Medical CenterMemphisUSA

Personalised recommendations