Title : Paradoxical allosteric effects of competitive inhibitors on neuronal alpha7 nicotinic receptor mutants - Bertrand_1997_Neuroreport_8_3591 |
Author(s) : Bertrand S , Devillers-Thiery A , Palma E , Buisson B , Edelstein SJ , Corringer PJ , Changeux JP , Bertrand D |
Ref : Neuroreport , 8 :3591 , 1997 |
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. |
PubMedSearch : Bertrand_1997_Neuroreport_8_3591 |
PubMedID: 9427332 |
Bertrand S, Devillers-Thiery A, Palma E, Buisson B, Edelstein SJ, Corringer PJ, Changeux JP, Bertrand D (1997)
Paradoxical allosteric effects of competitive inhibitors on neuronal alpha7 nicotinic receptor mutants
Neuroreport
8 :3591
Bertrand S, Devillers-Thiery A, Palma E, Buisson B, Edelstein SJ, Corringer PJ, Changeux JP, Bertrand D (1997)
Neuroreport
8 :3591