title: Arginine residue 120 of the human GABAA receptor alpha 1, subunit is essential for GABA binding and chloride ion current gating.
abstract: The effect of mutating the conserved amino acid residue arginine 120 to lysine in the GABAA receptor alpha 1 subunit was studied. In electrophysiological experiments, the arginine 120 lysine (R120K) mutation in the alpha 1 subunit, when co-expressed with beta 2 and gamma 2 subunits in Sf-9 insect cells, induces a 180-fold rightward shift of the GABA dose-response curve compared with wild type alpha 1 beta 2 gamma 2s GABAA receptors. The diazepam potentiation of GABA-gated chloride ion currents was not affected. The binding of the GABAA ligands [3H]muscimol and [3H]SR 95531 to alpha 1 (R120K) beta 2 gamma 2s GABAA receptors was abolished but the binding affinity of the benzodiazepine receptor ligand [3H]flunitrazepam was unchanged. These results suggest that the arginine residue 120 in the alpha 1 subtype of the GABAA receptor is essential for GABA binding.
authors.affiliation: Research Institute of Biological Psychiatry, Sct. Hans Hospital, Roskilde, Denmark.
authors.forename: S E
authors.initials: SE
authors.lastname: Westh-Hansen
authors.forename: M R
authors.initials: MR
authors.lastname: Witt
authors.forename: K
authors.initials: K
authors.lastname: Dekermendjian
authors.forename: T
authors.initials: T
authors.lastname: Liljefors
authors.forename: P B
authors.initials: PB
authors.lastname: Rasmussen
authors.forename: M
authors.initials: M
authors.lastname: Nielsen
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000235:genetics*; D002460:Cell Line; D018118:Chloride Channels / Q000502:physiology*; D004553:Electric Conductivity; D006801:Humans; D007313:Insecta / Q000166:cytology; D015640:Ion Channel Gating / Q000502:physiology*; D017354:Point Mutation / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018118:Chloride Channels; D020033:Protein Isoforms; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D001120:Arginine