title: Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor.
abstract: Site-directed mutagenesis and expression in Xenopus oocytes were used to study acetylcholine receptors in which serine residues (i) were replaced by alanines (alpha, delta subunits) or (ii) replaced a phenylalanine (beta subunit) at a postulated polar site within the M2 transmembrane helix. As the number of serines decreased, there were decreases in the residence time and consequently the equilibrium binding affinity of QX-222, a quaternary ammonium anesthetic derivative thought to bind within the open channel. Receptors with three serine-to-alanine mutations also displayed a selective decrease in outward single-channel currents. Both the direction of this rectification and the voltage dependence of QX-222 blockade suggest that the residues mutated are within the aqueous pore of the receptor and near its cytoplasmic (inner) surface.
authors: Division of Biology, California Institute of Technology, Pasadena 91125.
authors: R J
authors: RJ
authors: Leonard
authors: C G
authors: CG
authors: Labarca
authors: P
authors: P
authors: Charnet
authors: N
authors: N
authors: Davidson
authors: H A
authors: HA
authors: Lester
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D003001:Cloning, Molecular; D004553:Electric Conductivity; D005260:Female; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials; D009154:Mutation; D009865:Oocytes / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014981:Xenopus
chemical_list: D007473:Ion Channels; D012333:RNA, Messenger; D011978:Receptors, Nicotinic