Fig. 2.

3β5αP and 3β5βTHDOC reversed the effect of high concentrations of GABA potentiating steroids. A, Sample traces showing that 10 μm 3β5αP inhibited potentiation by high but not low concentrations of 3α5αP.B, Similar traces for 10 μm 3β5βTHDOC.C–E, Summary of effect of 3β5αP (C), 3β5βTHDOC (D), and 3β5βP (E) from oocytes tested with a range of 3α5αP concentrations. C, Summary of the effect of 10 μm 3β5αP against increasing concentrations of 3α5αP. Normalized responses in this and subsequent figures were calculated as follows: (I_M −I_N)/I_N, where I_M is the amplitude of the measured current in a given experimental condition, andI_N is the normalizing current. For these data and data in D and E,I_N was the response to 2 μmGABA in the absence of modulator. The solid linesrepresent least-squares fits of the data to the Hill equation as follows: I = I_max×Cⁿ/(EC₅₀ⁿ+ Cⁿ), where C is the concentration of potentiator, EC₅₀ is the concentration of potentiator that produced half-maximum potentiation, andn is the Hill coefficient. Parameters of the fit for potentiators in the absence (filled circles) and presence (open squares) of 3β5αP are given in Table 1. D, Summary of the effect of 10 μm 3β5βTHDOC under similar experimental conditions to those in C. E, Concentration–response relationship for 3α5αP in the presence and absence of 3β5βP (10 μm). F, Concentration–response relationship of the benzodiazepine agonist lorazepam in the presence and absence of the benzodiazepine antagonist flumazenil. The solid line through lorazepam concentration–response values (circles) is the best fit of the Hill equation, with an EC₅₀ of 76.7 nm and a Hill coefficient of 1.2 (n = 7). The solid line through lorazepam–flumazenil interaction values (squares) is the best fit of the Hill equation, with an EC₅₀ of 348.5 nm and a Hill coefficient of 1.1 (n = 7).