Modulation Of Recombinant Î±2* Î±3* Or Î±4*-Nicotinic Acetylcholine Receptor (Nachr) Function By Nachr Î²3 Subunits
The nicotinic acetylcholine receptor (nAChR) Î²3 subunit is thought to serve an accessory role in nAChR subtypes expressed in dopaminergic regions implicated in drug dependence and reward. When Î²3 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 Î±2, Î±3 or Î±4 plus either Î²2 or Î²4 subunits, that in the presumed presence of similar amounts of each nAChR subunit, co-expression with wild-type Î²3 subunits generally (except for Î±3*-nAChR) lowers amplitudes of agonist-evoked, inward peak currents by 20-50% without having dramatic effects (â‰¤ 2-fold) on agonist potencies. By contrast, co-expression with mutant Î² subunits generally (except for Î±4Î²2*-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 Î± subunit plus Î²4 and Î² subunits, there is spontaneous channel opening sensitive to blockade by the open channel blocker, atropine. Collectively, the results indicate that Î²3 subunits integrate into all of the studied receptor assemblies and suggest that natural co-expression with Î²3 subunits can influence levels of expression and agonist sensitivities of several nAChR subtypes. Â© 2012 International Society for Neurochemistry.
Journal of Neurochemistry
Digital Object Identifier (DOI)
Dash, Bhagirathi; Bhakta, Minoti; Chang, Yongchang; and Lukas, Ronald J., "Modulation Of Recombinant Î±2* Î±3* Or Î±4*-Nicotinic Acetylcholine Receptor (Nachr) Function By Nachr Î²3 Subunits" (2012). Translational Neuroscience. 60.