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 journalArticle

58 Citations (Scopus)

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

Fingerprint

Nicotinic Receptors
Bungarotoxins
Cholinergic Receptors
Threonine
Leucine
Mutation
methyllycaconitine

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Bertrand, S., Devillers-Thiéry, A., Palma, E., Buisson, B., Edelstein, S. J., Corringer, P. J., ... Bertrand, D. (1997). Paradoxical allosteric effects of competitive inhibitors on neuronal α7 nicotinic receptor mutants. NeuroReport, 8(16), 3591-3596.

Paradoxical allosteric effects of competitive inhibitors on neuronal α7 nicotinic receptor mutants. / Bertrand, Sonia; Devillers-Thiéry, Anne; Palma, Eleonora; Buisson, Bruno; Edelstein, Stuart J.; Corringer, Pierre Jean; Changeux, Jean Pierre; Bertrand, Daniel.

In: NeuroReport, Vol. 8, No. 16, 1997, p. 3591-3596.

Research output: Contribution to journalArticle

Bertrand, S, Devillers-Thiéry, A, Palma, E, Buisson, B, Edelstein, SJ, Corringer, PJ, Changeux, JP & Bertrand, D 1997, 'Paradoxical allosteric effects of competitive inhibitors on neuronal α7 nicotinic receptor mutants', NeuroReport, vol. 8, no. 16, pp. 3591-3596.
Bertrand S, Devillers-Thiéry A, Palma E, Buisson B, Edelstein SJ, Corringer PJ et al. Paradoxical allosteric effects of competitive inhibitors on neuronal α7 nicotinic receptor mutants. NeuroReport. 1997;8(16):3591-3596.
Bertrand, Sonia ; Devillers-Thiéry, Anne ; Palma, Eleonora ; Buisson, Bruno ; Edelstein, Stuart J. ; Corringer, Pierre Jean ; Changeux, Jean Pierre ; Bertrand, Daniel. / Paradoxical allosteric effects of competitive inhibitors on neuronal α7 nicotinic receptor mutants. In: NeuroReport. 1997 ; Vol. 8, No. 16. pp. 3591-3596.
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