NDLI: A human congenital myasthenia-causing mutation (εL78P) of the muscle nicotinic acetylcholine receptor with unusual single channel properties

Content Provider	PubMed Central
Author	Shelley, Christopher Colquhoun, David
Copyright Year	2005
Abstract	A mutation in the epsilon subunit of the human nicotinic acetylcholine receptor (εL78P) is known to cause a congenital slow channel myasthenic syndrome. We have investigated the changes in receptor function that result in the mutant receptor producing prolonged endplate currents, and consequent muscle damage. The rate constants for channel gating and for the binding and dissociation of acetylcholine were investigated by analysis of single ion channel recordings. A conventional mechanism with two non-equivalent binding sites, and variations upon this mechanism, were fitted to data using a maximum likelihood method that uses the Hawkes-Jalali-Colquhoun (HJC) treatment of missed brief events. The mutant receptor produced prolonged activations, bursts of openings that cause a slow decay of simulated synaptic currents. The main reason for the longer bursts of openings seen with mutant receptor was a decrease in the rate of ACh dissociation from diliganded receptors, though the lifetime of individual openings was somewhat increased too. As well as producing long bursts, the mutant receptor also produced many very short openings, though these carry little current. The burst structure for the mutant receptor at low ACh concentration is unusual in that most long bursts appear to start in a very brief monoliganded open state that then usually binds another ACh molecule to produce a long diliganded activation. The first opening is so short that it will usually be missed (together with the shut time that follows it), so the true burst length is likely to be underestimated.
Related Links	http://dx.doi.org/10.1113/jphysiol.2004.081497
Ending Page	396
Page Count	20
Starting Page	377
File Format	PDF
ISSN	00223751
e-ISSN	14697793
Journal	The Journal of Physiology
Issue Number	Pt 2
Volume Number	564
Language	English
Publisher	Blackwell Science Inc
Publisher Date	2005-04-01
Access Restriction	Open
Rights Holder	Blackwell Science Inc
Subject Keyword	Physiology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physiology Sports Science

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