The fifth subunit of the (α4β2)₂β2 nicotinic ACh receptor modulates maximal ACh responses

Abstract

This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc.

Potentiation of a neuronal nicotinic receptor via pseudo-agonist site

“…Our studies of concatemeric receptors show that each of the 2-4 subunit interfaces is required for potentiation, and that the contribution of each interface to potentiation is not equivalent. This functional asymmetry may originate from differences in the subunits that flank the 2-4 interfaces, as suggested in previous work in which mutations at nominally equivalent 4-2 subunit interfaces had different functional consequences [25,52]. For the 2-4 interface flanked by 4 and 2 subunits, the 2W176A mutation reduces the percentage of channel openings that are potentiated from 81 to 29.…”

“…Varying the ratio of α4 to β2 subunit cDNAs biases the receptor population toward a single subunit stoichiometry in both mammalian cell lines [15,25] and Xenopus laevis oocytes [13]. The amounts of transfected α4 and β2 cDNAs were respectively 3 and 0.3 μg for each 35 mm culture dish of cells.…”

A tale of ligands big and small: An update on how pentameric ligand-gated ion channels interact with agonists and proteins

“…in the allosteric constant) cannot be excluded, as the TMD of the two forms is different. However, work with concatenated subunits [46] shows that switching one TMD from β to α or vice versa has no effect on the sensitivity to ACh of the two types of channel. Conversely, the β/β interface has been confirmed to be non-functional, as mutating its aromatic box residues has essentially no effect on the 2-α receptor sensitivity to ACh.…”

Stoichiometry‐selective modulation of α4β2 nicotinic ACh receptors by divalent cations

“…To evaluate the effects of divalent cations on the kinetics of activation of the α4β2 nAChR, we recorded single-channel currents elicited by concentrations of ACh near the EC 50 for each stoichiometric form: 100 μM for the low-sensitivity (α4) 3 (β2) 2 stoichiometry and 10 μM for the high-sensitivity (α4) 2 (β2) 3 stoichiometry (Carbone et al, 2009;Harpsøe et al, 2011;Mazzaferro et al, 2011;Moroni et al, 2006;New et al, 2018). In the absence of divalent cations, both stoichio- For the (α4) 2 (β2) 3 stoichiometry, increasing the ACh concentration to 100 μM still did not produce clusters of channel openings (Figure S1).…”