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. 2013 Apr 25;169(2):371–383. doi: 10.1111/bph.12151

Figure 2.

Figure 2

Effects of compound 11 on GABA EC3 at wild-type and mutated α1β3 and at α1β3γ2 receptors. (A) Left trace: Individual current traces of GABA EC3 in the absence or presence of 10 μM compound 11 in α1β3 wild-type receptors and in α1β3 wild-type receptors pre-incubated with MTSEA-biotin (MB); Right trace: Individual current traces at GABA EC3 in the absence or presence of 10 μM compound 11 in α1V211Cβ3Q64C receptors and in α1V211Cβ3Q64C receptors treated (pre-incubated) with MTSEA-biotin (MB). (B) Concentration-response curves of compound 11 in wild-type α1β3 receptors (▪), α1β3 receptors pre-incubated with MTSEA-biotin (MB) (□), α1V211Cβ3Q64C receptors (•), and α1V211Cβ3Q64C receptors labelled by MTSEA-biotin (MB) (○).There was a slight reduction of compound 11 effect in mutated receptors (α1V211Cβ3Q64C) as compared with the wild-type α1β3 receptors. This effect was further significantly diminished after labelling of α1V211Cβ3Q64C receptors by MTSEA-biotin (100 nM − 30 μM; P < 0.001). (C) Concentration-dependent modulation of GABA EC3 control current by compound 11 in α1β3γ2 (▪), wild-type α1β3γ2 receptors pre-incubated with MTSEA-biotin (MB) (□), α1β3γ2M130C (•) and α1β3γ2M130C receptors pre-incubated with MTSEA-biotin (○). Data represent means ± SEM (n = 4–6) (D) Concentration-dependent modulation of α1β3γ2 receptors by compound 11 in the absence (▪) and the presence of 10 μM Ro15-1788 (□); the effect of Ro15-1788 on GABA EC3 current alone (•). The effect of compound 11 remained unchanged by the presence of Ro15-1788. Data represent means ± SEM (n = 4–5); (E) Individual current traces at GABA EC3 in the absence or presence of 1 μM diazepam, or 1 μM diazepam together with 50 nM compound 11. (F) Concentration-response curves for diazepam (▪), or for diazepam applied together with 50 nM compound 11 (•) or compound 30 (♦) and the effect of 50 nM compound 11 (□) or compound 30 (◇) on the GABA evoked EC3 current alone, all measured in the same cell expressing α1β3γ2 receptors. Compound 11 or compound 30 at 50 nM concentrations drastically inhibited the positive modulatory effect of diazepam (P < 0.001). All experiments were performed four to eight times in oocytes of different batches. Data represent means ± SEM.