Nicotinic acetylcholine receptors are allotter membrane proteins that belong to a large family of ligand-gated ion channels that mediate transmission in the cholinergic system. Structurally, it consists of five subunits of one of the four types alpha, beta, gamma and delta, with the alpha subunit is composed of nine possible subtypes (alpha 1-9) and four beta (beta-1-4). The binding of agonists to these receptors generates a sequence of conformational changes resulting in channel opening. Previously, this team at the Institute of Neurosciences of a joint center of the Miguel Hernandez University and the CSIC had shown that a residue of the alpha-7 nicotinic receptor, the aspartame in position 266 of the connecting sequence between Tran membrane domains M2 and M3, intervenes in the relationship between agonist binding and channel opening.

In fact, structural data indicate that this region may contain certain charged amino acids that participate in the mechanism involved in channel activation. The authors themselves raised in the present study, to test this hypothesis, so they replaced all charged residues of these loops (D142, D144, E45, L46, D128, R130 and D135) by other amino acids, determining the levels below of expression and electrophysiological responses to the mutant receptors. From his analysis shows that it is unlikely an opening mechanism controlled by the electrostatic interaction between two to two residues, but would rather a network of interactions between some of these residues that connects the binding of agonist to channel opening.