title: M2 pore mutations convert the glycine receptor channel from being anion- to cation-selective.
abstract: Three mutations in the M2 transmembrane domains of the chloride-conducting alpha1 homomeric glycine receptor (P250Delta, A251E, and T265V), which normally mediate fast inhibitory neurotransmission, produced a cation-selective channel with P(Cl)/P(Na), = 0.27 (wild-type P(Cl)/P(Na) = 25), a permeability sequence P(Cs) > P(K) > P(Na) > P(Li), an impermeability to Ca(2+), and a reduced glycine sensitivity. Outside-out patch measurements indicated reversed and accentuated rectification with extremely low mean single channel conductances of 3 pS (inward current) and 11 pS (outward current). The three inverse mutations, to those analyzed in this study, have previously been shown to make the alpha7 acetylcholine receptor channel anion-selective, indicating a common location for determinants of charge selectivity of inhibitory and excitatory ligand-gated ion channels.
authors.affiliation: School of Physiology and Pharmacology, University of New South Wales, Sydney 2052, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Keramidas
authors.forename: A J
authors.initials: AJ
authors.lastname: Moorhouse
authors.forename: C R
authors.initials: CR
authors.lastname: French
authors.forename: P R
authors.initials: PR
authors.lastname: Schofield
authors.forename: P H
authors.initials: PH
authors.lastname: Barry
mesh_terms: D000595:Amino Acid Sequence; D000838:Anions / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000235:genetics; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018408:Patch-Clamp Techniques; D018009:Receptors, Glycine / Q000235:genetics / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013379:Substrate Specificity / Q000235:genetics
chemical_list: D000838:Anions; D002412:Cations; D007473:Ion Channels; D018009:Receptors, Glycine; D012964:Sodium; D002118:Calcium