Paradoxical allosteric effects of competitive inhibitors on neuronal alpha7 nicotinic receptor mutants - Archive ouverte HAL Access content directly
Journal Articles NeuroReport Year : 1997

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

(1) , (2) , (1) , (1) , (1) , (2) , (2, 3) , (1)
1
2
3

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.
Not file

Dates and versions

pasteur-01718282 , version 1 (27-02-2018)

Identifiers

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

Cite

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

Altmetric

Share

Gmail Facebook Twitter LinkedIn More