title: A single amino acid exchange alters the pharmacology of neonatal rat glycine receptor subunit.
abstract: Agonist activation of the inhibitory glycine receptor (GlyR) in the adult vertebrate CNS is efficiently antagonized by the alkaloid strychnine. Here, we describe a novel rat GlyR alpha subunit cDNA (alpha 2*) that generates chloride channels of low strychnine sensitivity upon expression in Xenopus oocytes. Comparison with the highly homologous human alpha 2 polypeptide and site-directed mutagenesis identified a single amino acid exchange at position 167 that causes the altered pharmacology of alpha 2* receptors. Amplification by the polymerase chain reaction revealed a strong decrease in alpha 2* mRNA abundancy during postnatal spinal cord development. These data indicate that alpha 2* represents a ligand binding subunit of the previously identified neonatal GlyR isoform of low strychnine affinity.
authors.affiliation: Zentrum für Molekulare Biologie Heidelberg, Universität Heidelberg, Federal Republic of Germany.
authors.forename: J
authors.initials: J
authors.lastname: Kuhse
authors.forename: V
authors.initials: V
authors.lastname: Schmieden
authors.forename: H
authors.initials: H
authors.lastname: Betz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001483:Base Sequence; D018118:Chloride Channels; D004247:DNA / Q000235:genetics; D004594:Electrophysiology; D005260:Female; D015870:Gene Expression; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000502:physiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D013116:Spinal Cord / Q000254:growth & development / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection; D014981:Xenopus
chemical_list: D018118:Chloride Channels; D046911:Macromolecular Substances; D008565:Membrane Proteins; D012333:RNA, Messenger; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D004247:DNA