Modulation of recombinant, α2*, α3*or α4*-nicotinic acetylcholine receptor (nAChR) function by nAChR β3 subunits

The nicotinic acetylcholine receptor (nAChR) beta 3 subunit is thought to serve an accessory role in nAChR subtypes expressed in dopaminergic regions implicated in drug dependence and reward. When beta 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 a2, a3 or a4 plus either beta 2 or beta 4 subunits, that in the presumed presence of similar amounts of each nAChR subunit, co-expression with wild-type beta 3 subunits generally (except for a3*-nAChR) lowers amplitudes of agonist-evoked, inward peak currents by 2050% without having dramatic effects (= 2-fold) on agonist potencies. By contrast, co-expression with mutant beta 3V9S subunits generally (except for a4 beta 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 a subunit plus beta 4 and beta 3V9S subunits, there is spontaneous channel opening sensitive to blockade by the open channel blocker, atropine. Collectively, the results indicate that beta 3 subunits integrate into all of the studied receptor assemblies and suggest that natural co-expression with beta 3 subunits can influence levels of expression and agonist sensitivities of several nAChR subtypes.