Arginine residue 120 of the human GABAAreceptor α1subunit 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 GABAAreceptor α1subunit was studied. In electrophysiological experiments, the arginine 120 lysine (R120K) mutation in the α1subunit, when co-expressed with β2and γ2subunits in Sf-9 insect cells, induces a 180-fold rightward shift of the GABA dose–response curve compared with wild type α1β2γ2sGABAAreceptors. The diazepam potentiation of GABA-gated chloride ion currents was not affected. The binding of the GABAAligands [3H]muscimol and [3H]SR 95531 to α1(R120K)β2γ2sGABAAreceptors 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 α1subtype of the GABAAreceptor is essential for GABA binding.