Figure 3.

Concentration‐dependence of the effects of flupirtine on recombinant GABA_A receptors and comparison with K_v7 channels. Either GABA_A receptors composed of α1β2γ2S, α1β2δ and α4β3δ, respectively, or heteromeric K_v7.2/7.3 channels were expressed in tsA 201 cells, and currents were evoked either by the application of GABA concentrations corresponding to EC₅₀ values (Table 1) or by ramp hyperpolarizations from −20 to −60 mV (for K_v7 channels). Measurements were performed in the presence of either solvent (<1% DMSO) or the indicated concentrations of flupirtine. Peak amplitudes of GABA‐induced currents and K⁺ current amplitudes at −30 mV were determined respectively. Amplitudes in the presence of the indicated concentrations of flupirtine were normalized to the amplitudes in the presence of solvent. (A) Shows original sample traces of GABA‐evoked currents in presence of solvent (black trace) or 3 μM flupirtine (grey trace). (B) Depicts concentration‐response curves for currents through the indicated receptors (n = 5 to 6). Calculated values for α1β2γ2S receptors were 14.3 + 11.0 μM for EC₅₀ and 1.53 + 0.05 for maxima. For α1β2δ and α4β3δ receptors, maxima were fixed to the highest values determined (28.8 and 1.5, respectively); then, EC₅₀ values were calculated as 108 and 7 μM respectively. (C) A comparison of the effects of 3 and 10 μM flupirtine, respectively, on currents through either GABA_A receptors or K_v7 channels (n = 5 to 6); ** indicate significant differences versus solvent at P < 0.01; ## indicate significant differences versus all other values at P < 0.01.