Arginine residue 120 of the human GABAA receptor α1, subunit is essential for GABA binding and chloride ion current gating
1999; Lippincott Williams & Wilkins; Volume: 10; Issue: 11 Linguagem: Inglês
10.1097/00001756-199908020-00036
ISSN1473-558X
AutoresSvend-Erik Westh-Hansen, M R Witt, Kim Dekermendjian, Tommy Liljefors, P. B. Rasmussen, Mogens Brøndsted Nielsen,
Tópico(s)Neuroscience and Neuropharmacology Research
ResumoThe effect of mutating the conserved amino acid residue arginine 120 to lysine in the GABAA receptor α1 subunit was studied. In electrophysiological experiments, the arginine 120 lysine (R120K) mutation in the α1 subunit, when co-expressed with β2 and γ2 subunits in Sf-9 insect cells, induces a 180-fold rightward shift of the GABA dose–response curve compared with wild type α1β2γ2s 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 α1(R120K)β2γ2s 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 α1 subtype of the GABAA receptor is essential for GABA binding.
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