Gating of [alpha]3[beta]4 neuronal nicotinic receptor can be controlled by the loop M2-M3 of both [alpha]3 and [beta]4 subunits

• Published in: Pflügers Archiv Vol. 439; no. 1-2; p. 86
• Main Authors: Rovira, Jc, Vicente-agulló, F, Campos-caro, A, Criado, M, Sala, F, Sala, S, Ballesta, J J
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.12.1999
• Subjects: Proteins
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s004249900143

Previous studies have shown that the gating mechanism of α^sub 3^β^sub 4^ neuronal nicotinic receptors is affected by a residue in the middle of the M2-M3 loop of the β^sub 4^ subunit. We have extended the study of the same location to the α^sub 3^ subunit. Bovine α^sub 3^β^sub 4^ receptors were mutated in position 268, substituting the residue present in wild-type receptors, i.e. leucine in α^sub 3^ and asparagine in β^sub 4^, for an aspartate. Wild-type and mutated α^sub 3^and β^sub 4^ subunits were combined to form four different receptors. We have measured macroscopic currents in Xenopus oocytes elicited by nicotine, and related them to surface receptor expression measured with an epibatidine-binding essay. We also obtained single-channel recordings of the receptors to study their kinetic behaviour. The results were analysed in terms of an allosteric model with three states. We found that the effect of the mutation in the α^sub 3^ subunit on the gating of the receptor was similar to the corresponding mutation in the β^sub 4^ subunit. The effect when both subunits were mutated was additive, suggesting that the contribution of each subunit to the gating mechanism is independent.[PUBLICATION ABSTRACT]