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Paradoxical allosteric effects of competitive inhibitors on neuronal alpha7 nicotinic receptor mutants

Abstract : Mutation of the conserved leucine residue, in the second transmembrane domain of the neuronal alpha7 acetylcholine receptor to a threonine (L247T) causes pleiotropic alterations of receptor properties. In this study we examined the effects of competitive inhibitors on the alpha7-L247T physiological responses. While the alpha7 competitive inhibitor dihydro-beta-erythroidine evoked a current comparable to that induced by ACh, other inhibitors such as methyllycaconitine (MLA) and alpha-bungarotoxin (alpha-Bgt) caused a blockade of alpha7-L247T to ACh activation. When applied in the absence of ACh, MLA or alpha-Bgt reduced the cell leakage current, showing that alpha7-L247T displays a significant fraction (10%) of spontaneously open channels. These data can be interpreted in terms of an allosteric model, assuming that the L247T mutant possesses a low isomerization constant L and that MLA and alpha-Bgt stabilize the closed, resting state.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01718282
Contributor : Ana Cova Rodrigues <>
Submitted on : Tuesday, February 27, 2018 - 11:43:13 AM
Last modification on : Wednesday, October 14, 2020 - 4:05:03 AM

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  • HAL Id : pasteur-01718282, version 1
  • PUBMED : 9427332

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Sonia Bertrand, Anne Devillers-Thiéry, Eleonora Palma, Bruno Buisson, Stuart Edelstein, et al.. Paradoxical allosteric effects of competitive inhibitors on neuronal alpha7 nicotinic receptor mutants. NeuroReport, Lippincott, Williams & Wilkins, 1997, 8 (16), pp.3591-6. ⟨pasteur-01718282⟩

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