Serum choline activates mutant acetylcholine receptors that cause slow channel congenital myasthenic syndromes

Ming Zhou, Andrew G. Engel, Anthony Auerbach

Research output: Contribution to journalArticle

69 Scopus citations


We have found that mutant acetylcholine receptor channels (AChRs) that cause slow-channel congenital myasthenic syndromes are activated by serum and that the high frequency of openings in serum is reduced by treatment with choline oxidase. Thus, slow-channel congenital myasthenic syndrome AChRs at the neuromuscular junction are likely to be activated both by steady exposure to serum choline and by transient exposure to synaptically released transmitter. Single-channel kinetic analyses indicate that the increased response to choline is caused by a reduced intrinsic stability of the closed channel. The results suggest that a mutation that destabilizes the inactive conformation of the AChR, together with the sustained exposure of endplates to serum choline, results in continuous channel activity that contributes to the pathophysiology of the disease.

Original languageEnglish (US)
Pages (from-to)10466-10471
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number18
StatePublished - Aug 31 1999


ASJC Scopus subject areas

  • General

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