Modulation of recombinant, ?2*, ?3* or ?4*-nicotinic acetylcholine receptor (nAChR) function by nAChR ?3 subunits.

ABSTRACT: The nicotinic acetylcholine receptor (nAChR) ?3 subunit is thought to serve an accessory role in nAChR subtypes expressed in dopaminergic regions implicated in drug dependence and reward. When ?3 subunits are expressed in excess, they have a dominant-negative effect on function of selected nAChR subtypes. In this study, we show, in Xenopus oocytes expressing ?2, ?3 or ?4 plus either ?2 or ?4 subunits, that in the presumed presence of similar amounts of each nAChR subunit, co-expression with wild-type ?3 subunits generally (except for ?3*-nAChR) lowers amplitudes of agonist-evoked, inward peak currents by 20-50% without having dramatic effects (? 2-fold) on agonist potencies. By contrast, co-expression with mutant ?3(V9'S) subunits generally (except for ?4?2*-nAChR) increases agonist potencies, consistent with an expected gain-of-function effect. This most dramatically demonstrates formation of complexes containing three kinds of subunit. Moreover, for oocytes expressing nAChR containing any ? subunit plus ?4 and ?3(V9'S) subunits, there is spontaneous channel opening sensitive to blockade by the open channel blocker, atropine. Collectively, the results indicate that ?3 subunits integrate into all of the studied receptor assemblies and suggest that natural co-expression with ?3 subunits can influence levels of expression and agonist sensitivities of several nAChR subtypes.

SUBMITTER: Dash B 

PROVIDER: S-EPMC3569009 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature