Arginine residue 120 of the human GABAA receptor α1, subunit is essential for GABA binding and chloride ion current gating

THE effect of mutating the conserved amino acid residue arginine 120 to lysine in the GABA A receptor α 1 subunit was studied. In electrophysiological experiments, the arginine 120 lysine (R120K) mutation in the α 1 subunit, when co-expressed with β 2 and γ2 subunits in Sf-9 insect cells, induces a 180-fold rightward shift of the GABA dose-response curve compared with wild type α 1 β 2 γ 2s GABA A receptors. The diazepam potentiation of GABA-gated chloride ion currents was not affected. The binding of the GABA A ligands [ 3 H]muscimol and [ 3 H]SR 95531 to α 1 (R120K)β 2γ2 GABA A receptors was abolished but the binding affinity of the benzodiazepine receptor ligand [ 3 H]flunitrazepam was unchanged. These results suggest that the arginine residue 120 in the α 1 subtype of the GABA A receptor is essential for GABA binding.