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

Article Article scientifique Article Paradoxical allosteric effects of competitive inhibitors on neuronal α7 nicotinic receptor mutants eng 1997-11 author Bertrand Sonia 23091 author Devillers-Thiéry Anne author Palma Eleonora 96457 author Buisson Bruno 91186 author Edelstein Stuart 22770 Administration de la faculté des sciences (SIAD) author Corringer Pierre-Jean author Changeux Jean-Pierre author Bertrand Daniel 24727 Décanat et administration de la faculté de médecine (ADMED) 3591-3596 10.1097/00001756-199711100-00034 9427332 0959-4965 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. Acetylcholine Allosteric model Competitive antagonists Ligand-gated channels Nicotine Dewey 540 Dewey 610 39 Département de biochimie 144 3 Faculté de médecine 2 false Neuroreport 8 16 d95ac925-bc72-4ecf-8773-d55fb11bf51b Article (Published version) Restricted Bertrand_NR_199783591.pdf 354546 application/pdf b5b2656eec0cf57b41fa121706b67a44f779d05d55fe6a5cd07c9324e92c07bf restrictedAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie Faculté de médecine

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Paradoxical allosteric effects of competitive inhibitors on neuronal α7 nicotinic receptor mutants	Neuroreport			1997	91	0

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Buisson, Bruno