Figure 1.

GABA_A receptor current enhancement. (A, B) Two electrode voltage clamp was used to measure currents from oocytes injected with human α1β2γ2L GABA_A receptor subunits. Currents were elicited with 3 μM GABA (~EC₅) in the presence of increasing amounts of 6 (A) or propofol (B). Solid lines represent the nonlinear least-squares fit of the data. For 6: EC₅₀ = 4.5 ± 2.7 μM, nH = 1.4 ± 1.3, Imax = 22 ± 6% (4 oocytes). For propofol: EC₅₀ = 5.2 ± 2.1 μM, nH = 1.7 ± 1.2, Imax = 16 ± 3% (2 oocytes). Insets show current traces elicited by 3 μM GABA (black bars) plus increasing amounts of drug (1, 3, 10, 30, 100 μM 6 and 1, 3, 10, 30, 100, 300 μM propofol) (gray bars). (C, D) GABA concentration response curves shift to the left in the presence of drugs. For plotting, currents were normalized to I_GABA,max and [GABA] was normalized to the control GABA EC₅₀ for each experiment to minimize the effect of the spread of EC₅₀’s of the different oocytes.³⁸ The data was fit as described above and in the Experimental Section, for 6 (C): EC₅₀ = 0.99 ± 0.11, nH = 1.0 ± 0.1 for GABA alone (solid symbols) and EC₅₀ =0.12 ± 0.03, nH = 0.9 ± 0.2 in the presence of 6 μM 6 (open symbols) (3 oocytes). For propofol (D): EC₅₀ = 1.35 ± 0.2, nH = 0.9 ± 0.1 for GABA alone (solid symbols) and EC₅₀ = 0.12 ± 0.04, nH = 1.1 ± 0.3 in the presence of 4.4 μM propofol (open symbols) (4 oocytes).