PMID: 9539130Apr 16, 1998Paper

Mode switching kinetics produced by a naturally occurring mutation in the cytoplasmic loop of the human acetylcholine receptor epsilon subunit

Neuron
M MiloneA G Engel

Abstract

We describe the genetic and kinetic defects in a congenital myasthenic syndrome caused by heteroallelic mutations of the acetylcholine receptor (AChR) epsilon subunit gene. The mutations are an in-frame duplication of six residues in the long cytoplasmic loop (epsilon1254ins18) and a cysteine-loop null mutation (epsilonC128S). The epsilon1254 ins18 mutation causes mode switching in the kinetics of receptor activation in which three modes activate slowly and inactivate rapidly. The epsilon1245ins18-AChR at the endplate shows abnormally brief activation episodes during steady state agonist application and appears electrically silent during the synaptic response to acetylcholine. The phenotypic consequences are endplate AChR deficiency, simplification of the postsynaptic region, and compensatory expression of fetal AChR that restores electrical activity at the endplate and rescues the phenotype.

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Citations

Mar 15, 2000·Muscle & Nerve·J M Lindstrom
Jan 1, 2003·Muscle & Nerve·Andrew G EngelSteven M Sine
Mar 20, 2002·Current Neurology and Neuroscience Reports·Kinji Ohno, Andrew G Engel
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Oct 23, 1998·Journal of Physiology, Paris·A G EngelS M Sine
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Aug 17, 2011·The Journal of Biological Chemistry·Raman GoyalMichaela Jansen
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Nov 1, 2003·Annals of the New York Academy of Sciences·Andrew G EngelSteven M Sine
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Jun 13, 2018·Current Neurology and Neuroscience Reports·Andrew G Engel

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