Abstract
ANIMALS immunised with purified acetylcholine (ACh) receptor develop a muscular weakness much like that found in the human disease, myasthenia gravis1. This discovery led to the demonstration that myasthenia gravis is an autoimmune disease involving the production of antibodies against skeletal muscle ACh receptor2–5. Endplates from myasthenic patients have reduced miniature endplate potentials6, are less sensitive to ACh7,8 and have decreased amounts of ACh receptor9–11, much of which is bound by antibody10,12. In addition, there are substantial alterations in the ultrastructure of the synapse which may contribute to a loss in synaptic function11. We have previously demonstrated that sera from myasthenic patients reduce the ACh sensitivity of human skeletal muscle growing in tissue culture13. Our experiments demonstrated that this reduction in ACh sensitivity is due to two processes; an inactivation of ACh receptor function by antibody binding14 and a decrease in ACh receptor density resulting from an antibody-induced increase in the rate of ACh receptor degradation14–16. The stimulation of ACh receptor degradation by antibody is energy and temperature dependent14 and is similar to the phenomenon of antigenic modulation found in other systems17–19. Our previous experiments apply only to the ACh receptor found on muscle grown in tissue culture, a receptor which is presumably analogous to extrajunctional ACh receptor found in denervated muscle in vivo. Here we demonstrate that anti-receptor antiserum increases the rate of ACh receptor degradation in innervated as well as in denervated rat diaphragms maintained in organ culture.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Patrick, J. & Lindstrom, J. Science 180, 871–872 (1973).
Almon, R. R., Andrew, C. G. & Appel, S. H. Science 186, 55–57 (1973).
Bender, A. N., Ringel, S. P., Engel, W. K., Daniels, M. P. & Vogel, Z. Lancet i, 607–609 (1975).
Aharanov, A., Abramsky, O., Tarrab-Hazdai, R. & Fuchs, S. Lancet ii, 340–342 (1975).
Lindstrom, J. M., Lennon, V. A., Seybold, M. E. & Whittingham, S. Ann. N.Y. Acad. Sci. 274, 254–274 (1976).
Elmqvist, D., Hofmann, W. W., Kugelberg, J. & Quastel, D. M. J. J. Physiol., Lond. 174, 417–434 (1964).
Albuquerque, E. X., Rash, J. E., Mayer, R. F. & Sattersfield, J. R. Expl Neurol. 51, 536–563 (1976).
Albuquerque, E. X. et al. Ann. N.Y. Acad. Sci. 274, 475–492 (1976).
Fambrough, D. M., Drachman, D. B. & Satyamurti, S. Science 182, 293–295 (1973).
Lindstrom, J. & Lambert, E. Neurology 28, 130–138 (1978).
Engel, A. G., Lindstrom, J. M., Lambert, E. H. & Lennon, V. A. Neurology 27, 307–315 (1977).
Engel, A., Lambert, E. & Howard, G. Mayo Clinic Proc. 52, 267–280 (1977).
Bevan, S., Kullberg, R. W. & Heinemann, S. F. Nature 267, 263–265 (1977).
Heinemann, S., Bevan, S., Kullberg, R., Lindstrom, J. & Rice, J. Proc. natn. Acad. Sci. U.S.A. 74, 3090–3094 (1977).
Appel, S. H., Anwyl, R., McAdams, M. W. & Elias, S. Proc. natn. Acad. Sci. U.S.A. 74, 2130–2134 (1977).
Kao, I. & Drachman, D. B. Science 196, 527–529 (1977).
Lamm, M. E., Boyse, E. A., Old, L. J., Lisowska-Berstein, B. & Stockert, E. J. Immun. 101, 99–103 (1968).
Lesley, J. & Hyman, R. Eur. J. Immun. 4, 732–739 (1974).
Knopf, P. M., Destree, A. & Hyman, R. Eur. J. Immun. 3, 251–259 (1973).
Berg, D. K. & Hall, Z. W. J. Physiol., Lond. 252, 771–789 (1975).
Lee, C. Y., Tseng, L. F. & Chiu, T. H. Nature 215, 1177–1178 (1967).
Berg, D. K. & Hall, Z. W. Science 184, 473–475 (1974).
Merlie, J. P., Changeux, J. P. & Gros, F. Nature 264, 74–76 (1976).
Devreotes, P. N., Gardner, J. M. & Fambrough, D. M. Cell 10, 365–373 (1977).
Bevan, S., Heinemann, S., Lennon, V. A. & Lindstrom, J. Nature 260, 438–439 (1976).
Berg, D. K. & Hall, Z. J. Physiol., Lond. 252, 771–789 (1975).
Chuang, C. C. & Huang, M. C. Nature 253, 643–644 (1975).
Beranek, R. & Vyskocil, F. J. Physiol., Lond. 188, 53–66 (1967).
Brockes, J. P. & Hall, Z. Biochemistry 14, 2100–2106 (1975).
Neher, E. & Sakmann, B. Proc. natn. Acad. Sci. U.S.A. 72, 2140–2144 (1975).
Burden, S. Devl Biol. 57, 317–329 (1977).
Sahashi, K., Engel, A. G., Lindstrom, J., Lambert, E. H. & Lennon, V. J. Neuropath. exp. Neural. (in the press).
Lennon, V. A., Seybold, M. E., Lindstrom, J. M., Cochrane, C. & Ulevitch, R. J. exp. Med. 147, 973–983 (1977).
Anwyl, R., Appel, S. M. & Narahashi, T. Nature 267, 262–263 (1977).
Patrick, J., Lindstrom, J., Gulp, W. & McMillan, H. Proc. natn. Acad. Sci. U.S.A. 70, 3334–3338 (1973).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
HEINEMANN, S., MERLIE, J. & LINDSTROM, J. Modulation of acetylcholine receptor in rat diaphragm by anti-receptor sera. Nature 274, 65–68 (1978). https://doi.org/10.1038/274065a0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/274065a0
This article is cited by
-
Bortezomib: a proteasome inhibitor for the treatment of autoimmune diseases
Inflammopharmacology (2021)
-
Myasthenia gravis: An autoimmune response against the acetylcholine receptor
Immunologic Research (1993)
-
Specificities of autoantibodies in autoimmune receptor diseases
Immunologic Research (1988)
-
Phenotypic and functional analysis of lymphocytes in myasthenia gravis
Springer Seminars in Immunopathology (1985)
-
Induction of the morphologic changes of both acute and chronic experimental myasthenia by monoclonal antibody directed against acetylcholine receptor
Acta Neuropathologica (1984)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
