Abstract: Recombinant human GABAA receptors were investigated in vitro by coexpression of cDNAs coding for α1, β2 and γ2 subunits in the baculovirus/Sf-9 insect cell system. A single amino acid exchange α1 (asparatic acid 151 to asparagin or α1 (threonine 149 to glutamine) in the N-terminal, extracellular part of the α1 subunit induced about 10 fold decrease in an antagonist pitrazepine affinity. Other GABAA receptor ligands had little difference in their affinity. It was likely that 151 and 149 amino acid residues were essential for the binding affinity and efficacy of pitrazepine to GABAA receptor combinations containing an α1 subunit.

Key words: Recombinant human GABA_A receptor, α₁ subunit, Mutation, Pitrazepine