Non-equivalent ligand selectivity of agonist sites in (α4β2)2α4 nicotinic acetylcholine receptors: a key determinant of agonist efficacy.

ABSTRACT: The α4β2 nicotinic acetylcholine receptor (nAChR) is the most abundant nAChR type in the brain, and this receptor type exists in alternate (α4β2)2α4 and (α4β2)2β2 forms, which are activated by agonists with strikingly differing efficacies. Recent breakthroughs have identified an additional operational agonist binding site in the (α4β2)2α4 nAChR that is responsible for the signature sensitivity of this receptor to activation by agonists, yet the structural mechanisms determining agonist efficacy at this receptor type are not yet fully understood. In this study, we characterized the ligand selectivity of the individual agonist sites of the (α4β2)2α4 nAChR to determine whether differences in agonist selectivity influence agonist efficacy. Applying the substituted cysteine accessibility method

SUBMITTER: Mazzaferro S 

PROVIDER: S-EPMC4118137 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature