Fig. 1. Currents through constitutively active mutant α¹L264Tβ²γ^2Lγ-aminobutyric acid type A (GABA^A) receptors are modulated by benzodiazepine site ligands. (  A ) Currents from an oocyte expressing α¹L264Tβ²γ^2LGABA^Areceptors display constitutive activity in the absence of agonists. An apparently outward current is observed in the presence of 2 mm picrotoxin (PTX), which inhibits active channels. Inward currents from the same oocyte elicited with 1 mm γ-aminobutyric acid (GABA) before and after the picrotoxin exposure are also shown. (  B ) Diazepam elicits inward currents from an oocyte expressing α¹L264Tβ²γ^2LGABA^Areceptors. Traces are labeled with the diazepam (DZ) concentration. At 10 μm, diazepam initially elicits a smaller current than 1 μm diazepam, and a “surge” current is observed before deactivation. (  C ) Midazolam elicits inward currents from an oocyte expressing α¹L264Tβ²γ^2LGABA^Areceptors. Traces are labeled with the midazolam (MDZ) concentration. (  D ) FG7142, a benzodiazepine inverse agonist, reduces the activity of α¹L264Tβ²γ^2LGABA^Areceptors (apparent outward current), whereas flumazenil (FZ) elicits small inward currents. (  E ) Flumazenil (1 μm) elicits a small inward current and blocks further activation by 100 nm midazolam.