Fig. 4.
a Concentration–response curves for TETS inhibition of currents evoked by EC90 GABA for α2βxγ2L receptors to determine the changes induced by exchanging β2 for β3. The concentration response curve of TETS for α2β2γ2L (IC50 12.2 μM, 95% CI 10.5–15.8 μM, E max ~ 65%) was right-shifted in comparison with α2β3γ2L (IC50 480 nM, 95% CI 10.5–15.8 nM, E max ~ 80%). b Both the α6β1γ2L receptor (IC50 > 20 μM, E max ~ 25%) and the α6β2γ2L receptor (IC50 20 μM, 95% CI 18.3–21.7 μM, E max ~ 35%) showed a significantly reduced response to TETS. The α6β3γ2L receptor (IC50 400 nM, 95% CI 290–510 nM, E max ~ 70%) is highly sensitive to TETS as shown previously in Fig. 3. c α4β3γ2L receptor (IC50 1.82 μM, 95% CI 1.02–2.62 μM, E max ~ 46%, n H = 0.7) showed a reduced E max for TETS inhibition, while the α4β3δ receptor (IC50 3 μM, 95% CI 1.36–3.96 μM, E max ~ 85%, n H = 1.2) showed an increased Hill coefficient. d In α6 containing receptors (α6β3γ2L: IC50 400 nM, 95% CI 0.29–0.51 nM E max ~ 70% as previously shown), introduction of a δ subunit increased E max and reduced potency (α6β3δ: IC50 3.69 μM, 95% CI 3.18–4.2 μM, E max ~ 85%), while replacement of γ2L with γ1 right-shifted the concentration response curve (α6β3γ1: IC50 6.81 μM, 95% CI 3.9–9.7 μM, E max ~ 65%). Individual data points are presented as mean ± SD from 3–9 independent recordings. EC50 values are presented with 95% confidence intervals. Please note that the α4β3δ receptor combination was stably expressed in Lt-K cells, while the α6β3δ combination was transiently expressed in COS-7 cells