Accelerated degradation of acetylcholine receptor from cultured rat myotubes with myasthenia gravis sera and globulins

S. H. Appel, R. Anwyl, M. W. McAdams, S. Elias

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

Altered geometry of the neuromuscular junction and a decreased number of acetylcholine receptors appear responsible for the defect of neuromuscular transmission in myasthenia gravis. Cultured rat myotubes were used as a model to study in vitro the potential role of myasthenic globulins in the pathological process. Acetylcholine receptor content was assayed by the extent of 125I labeled α bungarotoxin binding, and acetylcholine receptor function was assayed by the sensitivity to acetylcholine iontophoresis. The half life of the acetylcholine receptor was 18.5 hr in the presence or absence of control sera. Myasthenic sera and globulins produced a gradual reduction in acetylcholine receptors, as assessed by biochemical and electrophysiological techniques. The half life in the presence of myasthenic sera was 6 hr. The accelerated turnover was unaffected by puromycin but was slowed by lowered temperature (18 to 20°), interference with energy metabolism (2,4 dinitrophenol), and interference with cytoskeletal structures (colchicine and cytochalasin B). No electrophysiological evidence was found to suggest globulin blockade of acetylcholine access to the acetylcholine receptor. Circulating globulins in myasthenia gravis may contribute to the functional defects of neuromuscular transmission by accelerating the rate of internalization and degradation of surface membrane acetylcholine receptors.

Original languageEnglish (US)
Pages (from-to)2130-2134
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume74
Issue number5
DOIs
StatePublished - 1977

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