Unraveling the high- and low-sensitivity agonist responses of nicotinic acetylcholine receptors.

ABSTRACT: The neuronal α4β2 nicotinic acetylcholine receptors exist as two distinct subtypes, (α4)(2)(β2)(3) and (α4)(3)(β2)(2), and biphasic responses to acetylcholine and other agonists have been ascribed previously to coexistence of these two receptor subtypes. We offer a novel and radical explanation for the observation of two distinct agonist sensitivities. Using different expression ratios of mammalian α4 and β2 subunits and concatenated constructs, we demonstrate that a biphasic response is an intrinsic functional property of the (α4)(3)(β2)(2) receptor. In addition to two high-sensitivity sites at α4β2 interfaces, the (α4)(3)(β2)(2) receptor contains a third low-sensitivity agonist binding site in the α4α4 interface. Occupation of this site is required for full activation and is responsible

SUBMITTER: Harpsoe K 

PROVIDER: S-EPMC6623092 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature