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Mechanisms of Anesthetic Action in Skeletal, Cardiac, and Smooth Muscle pp 57–69Cite as

Interactions of Fatty Acids with the Calcium Release Channel in Malignant Hyperthermia

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 301))

Abstract

The anesthesia-induced malignant hyperthermia (MH) syndrome has been suggested to be a consequence of a halothane-sensitive defect in Ca2+ regulation, based on muscle rigidity during the syndrome and the increase in Ca2+ in isolated fiber bundles exposed to halothane. Additionally, the threshold of Ca2+-induced Ca2+ release (TCICR) is lower than normal in isolated fractions of heavy sarcoplasmic reticulum (HSR) from porcine MH muscle.1,2 However, the defect need not reside in the Ca2+-release channel protein, as there are reports of nonrigid MH in humans3 and loss of Ca2+ regulation could be the result of a disturbance in fatty acid metabolism.4 The present study examines fatty acid metabolism and the influence of fatty acids on various aspects of Ca2+ regulation and on caffeine, halothane and succinylcholine action in normal and MH muscle. Additionally, since phenytoin has been suggested to antagonize MH,5 its effects on Ca2+ regulation and fatty acid metabolism have been examined.

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References

  1. T. E. Nelson, Abnormality in calcium release from skeletal sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia, J Clin Invest 72:862 (1983).

    Article  PubMed  CAS  Google Scholar 

  2. S. T. Ohnishi, S. Taylor, and G. A. Gronert, Calcium-induced Ca2+ release from sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia: the effects of halothane and dantrolene, FEBS Lett 161:103 (1983).

    Article  PubMed  CAS  Google Scholar 

  3. B. A. Britt and W. Kalow, Malignant hyperthermia: a statistical review, Can Anaesth Soc J 17:293 (1970).

    Article  PubMed  CAS  Google Scholar 

  4. J. E. Fletcher, L. Tripolitis, K. Erwin, S. Hanson, H. Rosenberg, P. A. Conti, and J. Beech, Fatty acids modulate calcium-induced calcium release from skeletal muscle heavy sarcoplasmic reticulum fractions: implications for malignant hyperthermia, Biochem Cell Biol 68:1195 (1990).

    Article  PubMed  CAS  Google Scholar 

  5. A. D. Korczyn, S. Shavit, and I. Shlosberg, The chick as a model for malignant hyperpyrexia, Eur J Pharmacol 61:187 (1980).

    Article  PubMed  CAS  Google Scholar 

  6. G. C. Allen, J. E. Fletcher, F. J. Huggins, P. A. Conti, and H. Rosenberg, Caffeine and halothane contracture testing in swine using the recommendations of the North American Malignant Hyperthermia Group, Anesthesiology 72:71 (1990).

    Article  PubMed  CAS  Google Scholar 

  7. H. Rosenberg and S. Reed, In vitro contracture tests for susceptibility to malignant hyperthermia, Anesth Analg 62:415 (1983).

    Article  PubMed  CAS  Google Scholar 

  8. J. E. Fletcher, H. Rosenberg, and F. H. Lizzo, Effects of droperidol, haloperidol and ketamine on halothane, succinylcholine and caffeine contractures: implications for malignant hyperthermia, Acta Anaesthesiot Scand 33:187 (1989).

    Article  CAS  Google Scholar 

  9. J. E. Fletcher, F. J. Huggins, and H. Rosenberg, The importance of calcium ions for in vitro malignant hyperthermia testing, Can J Anaesth 37:695 (1990).

    Article  PubMed  CAS  Google Scholar 

  10. J. E. Fletcher and H. Rosenberg, In vitro muscle contractures induced by halothane and suxamethonium: II. Human skeletal muscle from normal and malignant hyperthermia susceptible patients, Br J Anaesth 58:1433 (1986).

    Article  PubMed  CAS  Google Scholar 

  11. P. Palade, Drug-induced Ca2+ release from isolated sarcoplasmic reticulum. I. Use of pyrophosphate to study caffeine-induced Ca2+ release, J Biol Chem 262:6135 (1987).

    CAS  Google Scholar 

  12. A. Saito, S. Seiler, A. Chu, and S. Fleischer, Preparation and morphology of sarcoplasmic reticulum from rabbit skeletal muscle, J Cell Biol 99:875 (1984).

    Article  PubMed  CAS  Google Scholar 

  13. J. R. Mickelson, E. M. Gallant, L. A. Litterer, K. M. Johnson, W. E. Rempel, and C. F. Louis, Abnormal sarcoplasmic reticulum ryanodine receptor in malignant hyperthermia, J Biol Chem 263:9310 (1988).

    PubMed  CAS  Google Scholar 

  14. G. M. Vita, J. E. Fletcher, L. Tripolitis, P. A. Conti and H. Rosenberg, Ryanodine binding in swine correlates with strain differences, not malignant hyperthermia (MH) susceptibility, Anesthesiology 73:A460 (1990).

    Article  Google Scholar 

  15. J. E. Fletcher, K. Michaux, and M.-S. Jiang, Contribution of bee venom phospholipase A2 contamination in melittin fractions to presumed activation of tissue phospholipase A2, Toxicon 28:647 (1990).

    Article  PubMed  CAS  Google Scholar 

  16. J. E. Fletcher, K. Erwin, and L. J. Krueger, Fatty acid uptake and catecholamine-stimulated phospholipid metabolism in immortalized airway epithelial cells established from primary cultures, Biochem Int 21:733 (1990).

    PubMed  CAS  Google Scholar 

  17. J. E. Fletcher, H. Rosenberg, K. Michaux, K. S. Cheah, and A. M. Cheah, Lipid analysis of skeletal muscle from pigs susceptible to malignant hyperthermia, Biochem Cell Biol 66:917 (1988).

    Article  PubMed  CAS  Google Scholar 

  18. J. E. Fletcher, P. Kistler, H. Rosenberg, and K. M. Michaux, Dantrolene and mepacrine antagonize the hemolysis of human red blood cells by halothane and bee venom phospholipase A2, Toxicol Appl Pharmacol 90:410 (1987).

    Article  PubMed  CAS  Google Scholar 

  19. W. R. Morrison and L. M. Smith, Preparation of fatty acid methyl esters and dimethylacetals from lipids with boronfluoride-methanol, J Lipid Res 5:600 (1964).

    PubMed  CAS  Google Scholar 

  20. J. E. Fletcher, H. Rosenberg, K. Michaux, L. Tripolitis, and F. H. Lizzo, Triglycerides, not phospholipids, are the source of elevated free fatty acids in muscle from patients susceptible to malignant hyperthermia, Eur J Anaesth 6:355 (1989).

    CAS  Google Scholar 

  21. J. E. Fletcher, M.-S. Jiang, L. Tripolitis, L. A. Smith, and J. Beech, Interactions in red blood cells between fatty acids and either snake venom cardiotoxin or halothane, Toxicon 28:657 (1990).

    Article  PubMed  CAS  Google Scholar 

  22. S. J. Wieland, J. E. Fletcher, H. Rosenberg, and Q. H. Gong, Malignant hyperthermia: slow sodium current in cultured human muscle cells, Am J Physiol 257:C759 (1989).

    PubMed  CAS  Google Scholar 

  23. M. A. K. Markwell, S. M. Haas, L. I. Bieber, and N. E. Tolbert, A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples, Anal Biochem 87:206 (1978).

    Article  PubMed  CAS  Google Scholar 

  24. P. Stralfors, P. Bjorgell, and P. Belfrage, Hormonal regulation of hormone-sensitive lipase in intact adipocytes: identification of phosphorylated sites and effects on the phosphorylation by lipolytic hormones and insulin, Proc Natl Acad Sci 81:3317 (1984).

    Article  PubMed  CAS  Google Scholar 

  25. J. R. Mickelson, E. M. Gallant, W. E. Rempel, K. M. Johnson, L. A. Litterer, B. A. Jacobson, and C. F. Louis, Effects of the halothane-sensitivity gene on sarcoplasmic reticulum function, Am J Physiol 257:C781 (1989).

    PubMed  Google Scholar 

  26. K. S. Cheah and A. M. Cheah, Skeletal muscle mitochondrial phospholipase A2 and the interaction of mitochondria and sarcoplasmic reticulum in porcine malignant hyperthermia, Biochim Biophys Acta 638:40 (1981).

    Article  PubMed  CAS  Google Scholar 

  27. S. G. Laychock, Fatty acids and cyclooxygenase and lipoxygenase pathway inhibitors modulate inositol phosphate formation in pancreatic islets, Mol Pharmacol 37:928 (1990).

    PubMed  CAS  Google Scholar 

  28. P. S. Foster, E. Gesini, C. Claudianos, K. C. Hopkinson, and M. A. Denborough, Inositol 1,4,5,-trisphosphate phosphatase deficiency and malignant hyperpyrexia in swine, Lancet 1:124 (1989).

    Article  Google Scholar 

  29. J. W. Schmidt and W. A. Catterall, Palmitylation, sulfation, and glycosylation of the alpha subunit of the sodium channel. Role of post-translational modifications in channel assembly, J Biol Chem 262:13713 (1987).

    PubMed  CAS  Google Scholar 

  30. S. J. Wieland, J. E. Fletcher, Q. H. Gong, and H. Rosenberg, Unsaturated fatty acids modulate sodium current in cultured skeletal muscle, Soc Neurosci Abstr in press (1990).

    Google Scholar 

  31. L. H. Schlisefeld and M. Barany, Hydrolysis of phosphatidylethanolamine, phosphatidylcholine and glycerophosphoylcholine in skeletal muscle, Mol Physiol 7:165 (1985).

    Google Scholar 

  32. R. C. Levitt, V. A. McKusick, J. E. Fletcher, and H. Rosenberg, Gene candidate (letter), Nature 345:297 (1990).

    Article  PubMed  CAS  Google Scholar 

  33. T. V. McCarthy, J. M. S. Healy, J. J. A. Heffron, M. Lchane, T. Deufel, F. Lehmann-Horn, M. Farrall, and K. Johnson, Localisation of the malignant hyperthermia susceptibility locus to human chromosome 19ql2-13.2, Nature 343:562 (1990).

    Article  PubMed  CAS  Google Scholar 

  34. T. Stadler, W. Ebert, F. Kehlbach, E. Muller, and H. von Faber, Beta-adrenergic receptors and adenylate cyclase activity in heart, muscle and adipose tissue of German Landrace pigs selectively bred for differences in backfat deposition, Horm Metabol Res 22:145 (1990).

    Article  CAS  Google Scholar 

  35. G. Gandemer, G. Durand, and G. Pascal, Relative contribution of the main tissues and organs to body fatty acid synthesis in the rat, Lipids 18:223 (1983).

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Departments of Anesthesiology, Hahnemann University, Philadelphia, Pennsylvania, 19102-1192, USA

    Jeffrey E. Fletcher

  2. Departments of Biochemistry, Hahnemann University, Philadelphia, Pennsylvania, 19102-1192, USA

    Jeffrey E. Fletcher & Henry Rosenberg

  3. Department of Clinical Studies, University of Pennsylvania School of Veterinary Medicine, New Bolton Center, Kennett Square, Pennsylvania, 19348, USA

    Jill Beech

Authors
  1. Jeffrey E. Fletcher
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  2. Henry Rosenberg
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  3. Jill Beech
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Editors and Affiliations

  1. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, 21205, Baltimore, Maryland, USA

    Thomas J. J. Blanck  & David M. Wheeler  & 

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© 1991 Plenum Press, New York

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Fletcher, J.E., Rosenberg, H., Beech, J. (1991). Interactions of Fatty Acids with the Calcium Release Channel in Malignant Hyperthermia. In: Blanck, T.J.J., Wheeler, D.M. (eds) Mechanisms of Anesthetic Action in Skeletal, Cardiac, and Smooth Muscle. Advances in Experimental Medicine and Biology, vol 301. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5979-1_6

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  • DOI: https://doi.org/10.1007/978-1-4684-5979-1_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5981-4

  • Online ISBN: 978-1-4684-5979-1

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