title: A residue in the middle of the M2-M3 loop of the beta4 subunit specifically affects gating of neuronal nicotinic receptors.
abstract: An aspartate residue in the M2-M3 loop of neuronal nicotinic receptor alpha7 subunits is a major determinant of the channel functional response. This residue is conserved in most beta4 subunits, e.g. human and rat, but not in others, e.g. bovine. We have used these differences to examine the mechanism by which this residue alters the functional properties of alpha3beta4 receptors. Having ruled out an effect on the macroscopic binding ability of the agonist, the level of receptor expression, or the single channel conductance, the results suggest that receptors lacking that residue have a deficient coupling between binding and gating.
authors.affiliation: Departamento de Farmacología, Instituto de Neurociencias, Universidad Miguel Hernández, Campus de San Juan, Alicante, Spain.
authors.forename: J C
authors.initials: JC
authors.lastname: Rovira
authors.forename: J J
authors.initials: JJ
authors.lastname: Ballesta
authors.forename: F
authors.initials: F
authors.lastname: Vicente-Agulló
authors.forename: A
authors.initials: A
authors.lastname: Campos-Caro
authors.forename: M
authors.initials: M
authors.lastname: Criado
authors.forename: F
authors.initials: F
authors.lastname: Sala
authors.forename: S
authors.initials: S
authors.lastname: Sala
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002417:Cattle; D004553:Electric Conductivity; D005260:Female; D015870:Gene Expression; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000502:physiology*; D018722:Nicotinic Agonists / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D017354:Point Mutation; D011725:Pyridines / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship; D014316:Tritium; D014981:Xenopus
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D014316:Tritium; C082748:epibatidine