Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1978 Aug;41(8):746–753. doi: 10.1136/jnnp.41.8.746

Myasthenia gravis: further electrophysiological and ultrastructural analysis of transmission failure in the mouse passive transfer model.

K V Toyka, K L Birnberger, A P Anzil, C Schlegel, U Besinger, A Struppler
PMCID: PMC1083392  PMID: 210263

Abstract

Using the mouse passive transfer model the mean amplitude of miniature endplate potentials and endplate potentials of mice treated with myasthenic immunoglobulins was markedly decreased. Miniature endplate potential frequency and quantum content of endplate potentials were normal, arguing against a major presynaptic disarrangement. Under electron-microscopy no gross structural alterations of endplates were demonstrated. It is concluded that the mouse passive transfer model closely resembles human myasthenia gravis of recent onset.

Full text

PDF
746

Images in this article

750Image
on p.750

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aharonov A., Abramsky O., Tarrab-Hazdai R., Fuchs S. Humoral antibodies to acetylcholine receptor in patients with myasthenia gravis. Lancet. 1975 Aug 23;2(7930):340–342. doi: 10.1016/s0140-6736(75)92779-8. [DOI] [PubMed] [Google Scholar]
  2. Albuquerque E. X., Rash J. E., Mayer R. F., Satterfield J. R. An electrophysiological and morphological study of the neuromuscular junction in patients with myasthenia gravis. Exp Neurol. 1976 Jun;51(3):536–563. doi: 10.1016/0014-4886(76)90179-5. [DOI] [PubMed] [Google Scholar]
  3. Almon R. R., Andrew C. G., Appel S. H. Serum globulin in myasthenia gravis: inhibition of alpha-bungarotoxin binding to acetylcholine receptors. Science. 1974 Oct 4;186(4158):55–57. doi: 10.1126/science.186.4158.55. [DOI] [PubMed] [Google Scholar]
  4. Anwyl R., Appel S. M., Narahashi T. Myasthenia gravis serum reduces acetylcholine sensitivity in cultured rat myotubes. Nature. 1977 May 19;267(5608):262–263. doi: 10.1038/267262a0. [DOI] [PubMed] [Google Scholar]
  5. Appel S. H., Anwyl R., McAdams M. W., Elias S. Accelerated degradation of acetylcholine receptor from cultured rat myotubes with myasthenia gravis sera and globulins. Proc Natl Acad Sci U S A. 1977 May;74(5):2130–2134. doi: 10.1073/pnas.74.5.2130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. BOYD I. A., MARTIN A. R. The end-plate potential in mammalian muscle. J Physiol. 1956 Apr 27;132(1):74–91. doi: 10.1113/jphysiol.1956.sp005503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bender A. N., Ringel S. P., Engel W. K., Daniels M. P., Vogel Z. Myasthenia gravis: a serum factor blocking acetylcholine receptors of the human neuromuscular junction. Lancet. 1975 Mar 15;1(7907):607–609. doi: 10.1016/s0140-6736(75)91886-3. [DOI] [PubMed] [Google Scholar]
  8. Bevan S., Kullberg R. W., Heinemann S. F. Human myasthenic sera reduce acetylcholine sensitivity of human muscle cells in tissue culture. Nature. 1977 May 19;267(5608):263–265. doi: 10.1038/267263a0. [DOI] [PubMed] [Google Scholar]
  9. Changeux J. P., Benedetti L., Bourgeois J. P., Brisson A., Cartaud J., Devaux P., Grünhagen H., Moreau M., Popot J. L., Sobel A. Some structural properties of the cholinergic receptor protein in its membrane environmental relevant to its function as a pharmacological receptor. Cold Spring Harb Symp Quant Biol. 1976;40:211–230. doi: 10.1101/sqb.1976.040.01.023. [DOI] [PubMed] [Google Scholar]
  10. ELMQVIST D., HOFMANN W. W., KUGELBERG J., QUASTEL D. M. AN ELECTROPHYSIOLOGICAL INVESTIGATION OF NEUROMUSCULAR TRANSMISSION IN MYASTHENIA GRAVIS. J Physiol. 1964 Nov;174:417–434. doi: 10.1113/jphysiol.1964.sp007495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Engel A. G., Lambert E. H., Howard F. M. Immune complexes (IgG and C3) at the motor end-plate in myasthenia gravis: ultrastructural and light microscopic localization and electrophysiologic correlations. Mayo Clin Proc. 1977 May;52(5):267–280. [PubMed] [Google Scholar]
  12. Engel A. G., Lindstrom J. M., Lambert E. H., Lennon V. A. Ultrastructural localization of the acetylcholine receptor in myasthenia gravis and in its experimental autoimmune model. Neurology. 1977 Apr;27(4):307–315. doi: 10.1212/wnl.27.4.307. [DOI] [PubMed] [Google Scholar]
  13. Engel A. G., Santa T. Histometric analysis of the ultrastructure of the neuromuscular junction in myasthenia gravis and in the myasthenic syndrome. Ann N Y Acad Sci. 1971 Sep 15;183:46–63. doi: 10.1111/j.1749-6632.1971.tb30741.x. [DOI] [PubMed] [Google Scholar]
  14. Engel A. G., Tsujihata M., Lindstrom J. M., Lennon V. A. The motor end plate in myasthenia gravis and in experimental autoimmune myasthenia gravis. A quantitative ultrastructural study. Ann N Y Acad Sci. 1976;274:60–79. doi: 10.1111/j.1749-6632.1976.tb47676.x. [DOI] [PubMed] [Google Scholar]
  15. Fambrough D. M., Drachman D. B., Satyamurti S. Neuromuscular junction in myasthenia gravis: decreased acetylcholine receptors. Science. 1973 Oct 19;182(4109):293–295. doi: 10.1126/science.182.4109.293. [DOI] [PubMed] [Google Scholar]
  16. Feltkamp T. E., van den Berg-Loonen P. M., Nijenhuis L. E., Engelfriet C. P., van Rossum A. L., van Loghem J. J., Oosterhuis H. J. Myasthenia gravis, autoantibodies, and HL-A antigens. Br Med J. 1974 Jan 26;1(5899):131–133. doi: 10.1136/bmj.1.5899.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Granato D. A., Fulpius B. W., Moody J. F. Experimental myasthenia in Balb/c mice immunized with rat acetylcholine receptor from rat denervated muscle. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2872–2876. doi: 10.1073/pnas.73.8.2872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Green D. P., Miledi R., Vincent A. Neuromuscular transmission after immunization against acetylcholine receptors. Proc R Soc Lond B Biol Sci. 1975 Apr 29;189(1094):57–68. doi: 10.1098/rspb.1975.0041. [DOI] [PubMed] [Google Scholar]
  19. Kao I., Drachman D. B. Myasthenic immunoglobulin accelerates acetylcholine receptor degradation. Science. 1977 Apr 29;196(4289):527–529. doi: 10.1126/science.850793. [DOI] [PubMed] [Google Scholar]
  20. Lambert E. H., Lindstrom J. M., Lennon V. A. End-plate potentials in experimental autoimmune myasthenia gravis in rats. Ann N Y Acad Sci. 1976;274:300–318. doi: 10.1111/j.1749-6632.1976.tb47694.x. [DOI] [PubMed] [Google Scholar]
  21. Lennon V. A. Immunology of the acetylcholine receptor. Immunol Commun. 1976;5(4):323–344. doi: 10.3109/08820137609044283. [DOI] [PubMed] [Google Scholar]
  22. Lindstrom J. M., Engel A. G., Seybold M. E., Lennon V. A., Lambert E. H. Pathological mechanisms in experimental autoimmune myasthenia gravis. II. Passive transfer of experimental autoimmune myasthenia gravis in rats with anti-acetylcholine recepotr antibodies. J Exp Med. 1976 Sep 1;144(3):739–753. doi: 10.1084/jem.144.3.739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lindstrom J. M., Seybold M. E., Lennon V. A., Whittingham S., Duane D. D. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology. 1976 Nov;26(11):1054–1059. doi: 10.1212/wnl.26.11.1054. [DOI] [PubMed] [Google Scholar]
  24. Mittag T., Kornfeld P., Tormay A., Woo C. Detection of anti-acetylcholine receptor factors in serum and thymus from patients with myasthenia gravis. N Engl J Med. 1976 Mar 25;294(13):691–694. doi: 10.1056/NEJM197603252941303. [DOI] [PubMed] [Google Scholar]
  25. Patrick J., Lindstrom J. Autoimmune response to acetylcholine receptor. Science. 1973 May 25;180(4088):871–872. doi: 10.1126/science.180.4088.871. [DOI] [PubMed] [Google Scholar]
  26. Pirskanen R. On the significance of HL-A and LD antigens in myasthenia gravis. Ann N Y Acad Sci. 1976;274:451–460. doi: 10.1111/j.1749-6632.1976.tb47706.x. [DOI] [PubMed] [Google Scholar]
  27. Rash J. E., Albuquerque E. X., Hudson C. S., Mayer R. F., Satterfield J. R. Studies of human myasthenia gravis: electrophysiological and ultrastructural evidence compatible with antibody attachment to acetylcholine receptor complex. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4584–4588. doi: 10.1073/pnas.73.12.4584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sanders D. B., Schleifer L. S., Eldefrawi M. E., Norcross N. L., Cobb E. E. An immunologically induced defect of neuromuscular transmission in rats and rabbits. Ann N Y Acad Sci. 1976;274:319–336. doi: 10.1111/j.1749-6632.1976.tb47695.x. [DOI] [PubMed] [Google Scholar]
  29. Tarrab-Hazdai R., Aharonov A., Silman I., Fuchs S., Abramsky O. Experimental autoimmune myasthenia induced in monkeys by purified acetylcholine receptor. Nature. 1975 Jul 10;256(5513):128–130. doi: 10.1038/256128a0. [DOI] [PubMed] [Google Scholar]
  30. Thornell L. E., Sjöström M., Mattsson C. H., Heilbronn E. Morphological observations on motor end-plates in rabbits with experimental myasthenia. J Neurol Sci. 1976 Oct;29(2-4):389–410. doi: 10.1016/0022-510x(76)90187-8. [DOI] [PubMed] [Google Scholar]
  31. Toyka K. V., Brachman D. B., Pestronk A., Kao I. Myasthenia gravis: passive transfer from man to mouse. Science. 1975 Oct 24;190(4212):397–399. doi: 10.1126/science.1179220. [DOI] [PubMed] [Google Scholar]
  32. Toyka K. V., Drachman D. B., Griffin D. E., Pestronk A., Winkelstein J. A., Fishbeck K. H., Kao I. Myasthenia gravis. Study of humoral immune mechanisms by passive transfer to mice. N Engl J Med. 1977 Jan 20;296(3):125–131. doi: 10.1056/NEJM197701202960301. [DOI] [PubMed] [Google Scholar]
  33. Wekerle H., Ketelsen U. P. Intrathymic pathogenesis and dual genetic control of myasthenia gravis. Lancet. 1977 Mar 26;1(8013):678–680. doi: 10.1016/s0140-6736(77)92118-3. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES