Table 1.

Summary of GABA, flurazepam, and zolpidem concentration–response data from WT and mutant α 1β 2γ 2 receptors

ReceptorGABAFlurazepamZolpidem
EC50m)nHnMaximum potentiationEC50 (nm)nHnMaximum potentiationEC50 (nm)nHn
αβγ26.4 ± 5.51.2 ± 0.272.58 ± 0.25272 ± 451.0 ± 0.184.46 ± 0.26335 ± 580.8 ± 0.07
αβγQ182C29.3 ± 4.21.4 ± 0.332.23 ± 0.06163 ± 101.0 ± 0.134.06 ± 0.51237 ± 170.9 ± 0.14
αβγW183C24.1 ± 2.61.5 ± 0.230.55 ± 0.06**303 ± 1001.3 ± 0.131.54 ± 0.30**376 ± 630.9 ± 0.25
αβγK184C28.0 ± 6.91.5 ± 0.152.59 ± 0.24208 ± 371.0 ± 0.034.88 ± 0.33442 ± 1210.8 ± 0.13
αβγR185C10.7 ± 3.5**1.5 ± 0.332.81 ± 0.26214 ± 271.1 ± 0.134.42 ± 0.61260 ± 451.0 ± 0.13
αβγS186C23.0 ± 4.01.4 ± 0.032.36 ± 0.18244 ± 201.0 ± 0.034.46 ± 0.43592 ± 47**0.8 ± 0.14
αβγS187C21.6 ± 3.51.6 ± 0.132.44 ± 0.25257 ± 741.0 ± 0.135.04 ± 0.66299 ± 310.8 ± 0.03
αβγV188C22.8 ± 6.01.4 ± 0.132.74 ± 0.17253 ± 611.0 ± 0.034.75 ± 0.15436 ± 460.8 ± 0.13
αβγE189C16.6 ± 6.21.5 ± 0.141.48 ± 0.14**554 ± 108**0.9 ± 0.144.14 ± 0.63679 ± 45**0.9 ± 0.14
αβγV190C24.0 ± 3.41.6 ± 0.143.22 ± 0.31**434 ± 32**1.1 ± 0.234.22 ± 0.44333 ± 320.9 ± 0.13
αβγG191C11.1 ± 2.3**1.6 ± 0.243.83 ± 0.41**675 ± 120**1.1 ± 0.144.49 ± 0.25439 ± 950.9 ± 0.13
αβγD192C17.3 ± 3.51.5 ± 0.232.00 ± 0.25**282 ± 870.9 ± 0.143.85 ± 0.19283 ± 590.9 ± 0.13
αβγT193C23.7 ± 4.01.5 ± 0.232.67 ± 0.17348 ± 551.0 ± 0.134.27 ± 0.06309 ± 330.9 ± 0.03
αβγR194C11.0 ± 4.2**1.4 ± 0.232.39 ± 0.24238 ± 641.0 ± 0.263.12 ± 0.22*173 ± 46*1.0 ± 0.13
αβγS195C29.6 ± 2.11.3 ± 0.132.02 ± 0.28**183 ± 781.1 ± 0.143.35 ± 0.53*192 ± 13*0.9 ± 0.03
αβγW196C10.3 ± 2.1**1.1 ± 0.232.26 ± 0.12357 ± 471.1 ± 0.254.37 ± 0.51374 ± 370.8 ± 0.13
αβγR197C17.4 ± 4.71.2 ± 0.140.64 ± 0.12**114 ± 43*1.2 ± 0.031.46 ± 0.20**92 ± 13**1.0 ± 0.13
  • EC50 values were derived by nonlinear regression of the concentration–response data as described in Materials and Methods. Flurazepam and zolpidem potentiation of IGABA (EC2–5) was calculated as follows: [(IGABA + BZD/IGABA) − 1]. Maximum potentiation values represent potentiation in the presence of 3 μ m FZM and 10 μ m ZPM, respectively. Data represent mean ± SD from n experiments. nH, Calculated Hill coefficient. Values significantly different from WT receptors are indicated (*p < 0.05; **p < 0.01).