Effect of alanine substitution at α1 Lys104 and γ2 Asp75 on GABA sensitivity and benzodiazepine responses.
A, GABA concentration-response curves of WT, α1(K104A)β2γ2, α1β2γ2(D75A), and α1(K104A)β2γ2(D75A) receptors. The concentration-response curves were significantly different (F(21,132) = 1.937, p < 0.05). Each symbol represents the data from three to six oocytes, and error bars represent the S.E. In some cases, error bars fall within symbols. B, bar graph comparing levels of diazepam and flunitrazepam potentiation between WT and alanine-substituted receptors. Potentiation of GABA EC5–10 by 1 μm diazepam and 1 μm flunitrazepam was decreased for single but not double alanine substitution mutants compared with WT receptors. A one-way ANOVA revealed a significant effect of mutant on receptor potentiation by diazepam (F(3,23) = 51.407, p < 0.001) and flunitrazepam (F(3,19) = 26.926, p < 0.001). Each symbol represents the percent potentiation observed in one oocyte, and each bar represents the mean percent potentiation. Error bars represent the S.E.