Sites of positive allosteric modulation by neurosteroids on ionotropic γ-aminobutyric acid receptor subunits

AbstractNeurosteroids are known as allosteric modulators of ionotropic γ-aminobutyric acid (GABA) receptors. Here, we investigated sites of positive allosteric modulation by allotetrahydrodeoxycorticosterone (5α-THDOC) at GABA receptors using the technique of chimeragenesis and the Xenopus oocyte expression system. Our findings have demonstrated that the region from transmembrane segment (TM) 4 to the C-terminus of the GABAA receptor α1 subunit is crucial for the action of 5α-THDOC, but insufficient for the action of another neurosteroid allopregnanolone, suggesting that a specific region critical for neurosteroid action at GABA receptors exists in the domain between TM4 and the C-terminus of GABA receptor subunits