title: Role of the putative transmembrane segment M3 in gating of neuronal nicotinic receptors.
abstract: The involvement of some structural domains in the gating of the neuronal nicotinic acetylcholine receptor (AChR) was studied by expressing functional alpha7/alpha3 chimeric subunits in Xenopus oocytes. Substitution of the M3 transmembrane segment in the alpha7 subunit modifies the kinetic properties of the chimeric AChRs as follows: (a) a 6-fold reduction in the maximal current evoked by nicotinic agonists, (b) a 10-fold decrease in the macroscopic desensitization rate, (c) an increase of almost 1 order of magnitude in the apparent affinity for acetylcholine and nicotine, and (d) a decrease in the affinity for alpha-bungarotoxin. Computer simulations showed that the first three effects could be accounted for by a simple kinetic model in which chimeric AChRs presented a smaller ratio of the gating rates, beta/alpha, and a slightly slower desensitization rate. It is concluded that the M3 domain influences the gating of neuronal AChRs.
authors.affiliation: Departamento de Neuroquímica, Universidad de Alicante, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Campos-Caro
authors.forename: J C
authors.initials: JC
authors.lastname: Rovira
authors.forename: F
authors.initials: F
authors.lastname: Vicente-Agulló
authors.forename: J J
authors.initials: JJ
authors.lastname: Ballesta
authors.forename: S
authors.initials: S
authors.lastname: Sala
authors.forename: M
authors.initials: M
authors.lastname: Criado
authors.forename: F
authors.initials: F
authors.lastname: Sala
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D003198:Computer Simulation; D015640:Ion Channel Gating / Q000502:physiology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship; D014981:Xenopus
chemical_list: D002038:Bungarotoxins; D011978:Receptors, Nicotinic