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

Abstract

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.

• Authors: M Zhou, A G Engel, A Auerbach
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 96 Issue 18 Pg. 10466-71 (Aug 31 1999) ISSN: 0027-8424 [Print] United States
• PMID: 10468632 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Cholinergic
• Choline

Topics

• Animals
• Cell Line
• Choline (blood)
• Humans
• Kidney
• Membrane Potentials
• Mice
• Mutation
• Myasthenia Gravis (congenital, genetics, physiopathology)
• Patch-Clamp Techniques
• Point Mutation
• Receptors, Cholinergic (genetics, physiology)
• Syndrome
• Transfection