A single amino acid exchange alters the pharmacology of neonatal rat glycine receptor subunit.
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.
Kuhse
J
J
Zentrum für Molekulare Biologie Heidelberg, Universität Heidelberg, Federal Republic of Germany.
Schmieden
V
V
Betz
H
H
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
D018118:Chloride Channels; D046911:Macromolecular Substances; D008565:Membrane Proteins; D012333:RNA, Messenger; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D004247:DNA