Molecular NeuroscienceParadoxical allosteric effects of competitive inhibitors on neuronal α7 nicotinic receptor mutantsBertrand, Sonia1; Devillers-Thiéry, Anne3; Palma, Eleonora1,4; Buisson, Bruno1; Edelstein, Stuart J.2; Corringer, Pierre-Jean3; Changeux, Jean-Pierre3; Bertrand, Daniel1,5Author Information 1Departments of Physiology, Medical Faculty, CMU, 1 rue Michel Servet, CH1211 Geneva 4, Switzerland 2Departments of Biochemistry, Medical Faculty, CMU, 1 rue Michel Servet, CH1211 Geneva 4, Switzerland 3URA CNRS D1284, Neurobiologie Moléculaire, Institut Pasteur, 75724 Paris Cedex 15, France. 4Present address: Regina Elena Cancer Institute, Biofisica, 1-00158 Roma, Italy 5Corresponding Author: Daniel Bertrand Received 18 July 1997; accepted 21 August 1997 NeuroReport: November 10th, 1997 - Volume 8 - Issue 16 - p 3591-3596 Buy 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. © Lippincott-Raven Publishers.