Paradoxical allosteric effects of competitive inhibitors on neuronal α7 nicotinic receptor mutants

Sonia Bertrand, Anne Devillers-Thiéry, Eleonora Palma, Bruno Buisson, Stuart J. Edelstein, Pierre Jean Corringer, Jean Pierre Changeux, Daniel Bertrand

Research output: Contribution to journalArticlepeer-review

Abstract

Mutation of the conserved leucine residue, in the second transmembrane domain of the neuronal α7 acetylcholine receptor to a threonine (L247T) causes pleiotropic alterations of receptor properties. In this study we examined the effects of competitive inhibitors on the α7-L247T physiological responses. While the α7 competitive inhibitor dihydro-β-erythroidine evoked a current comparable to that induced by ACh, other inhibitors such as methyllycaconitine (MLA) and α-bungarotoxin (α-Bgt) caused a blockade of α7-L247T to ACh activation. When applied in the absence of ACh, MLA or α- Bgt reduced the cell leakage current showing that α7-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 α-Bgt stabilize the closed, resting state.

Original languageEnglish
Pages (from-to)3591-3596
Number of pages6
JournalNeuroReport
Volume8
Issue number16
Publication statusPublished - 1997

Keywords

  • Acetylcholine
  • Allosteric model
  • Competitive antagonists
  • Ligand-gated channels
  • Nicotine

ASJC Scopus subject areas

  • Neuroscience(all)

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