Table 1.
Summary of GABA, flurazepam, and zolpidem concentration–response data from WT and mutant α 1β 2γ 2 receptors
| Receptor | GABA |
Flurazepam |
Zolpidem |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| EC50 (μm) | nH | n | Maximum potentiation | EC50 (nm) | nH | n | Maximum potentiation | EC50 (nm) | nH | n | |
| αβγ | 26.4 ± 5.5 | 1.2 ± 0.2 | 7 | 2.58 ± 0.25 | 272 ± 45 | 1.0 ± 0.1 | 8 | 4.46 ± 0.26 | 335 ± 58 | 0.8 ± 0.0 | 7 |
| αβγQ182C | 29.3 ± 4.2 | 1.4 ± 0.3 | 3 | 2.23 ± 0.06 | 163 ± 10 | 1.0 ± 0.1 | 3 | 4.06 ± 0.51 | 237 ± 17 | 0.9 ± 0.1 | 4 |
| αβγW183C | 24.1 ± 2.6 | 1.5 ± 0.2 | 3 | 0.55 ± 0.06** | 303 ± 100 | 1.3 ± 0.1 | 3 | 1.54 ± 0.30** | 376 ± 63 | 0.9 ± 0.2 | 5 |
| αβγK184C | 28.0 ± 6.9 | 1.5 ± 0.1 | 5 | 2.59 ± 0.24 | 208 ± 37 | 1.0 ± 0.0 | 3 | 4.88 ± 0.33 | 442 ± 121 | 0.8 ± 0.1 | 3 |
| αβγR185C | 10.7 ± 3.5** | 1.5 ± 0.3 | 3 | 2.81 ± 0.26 | 214 ± 27 | 1.1 ± 0.1 | 3 | 4.42 ± 0.61 | 260 ± 45 | 1.0 ± 0.1 | 3 |
| αβγS186C | 23.0 ± 4.0 | 1.4 ± 0.0 | 3 | 2.36 ± 0.18 | 244 ± 20 | 1.0 ± 0.0 | 3 | 4.46 ± 0.43 | 592 ± 47** | 0.8 ± 0.1 | 4 |
| αβγS187C | 21.6 ± 3.5 | 1.6 ± 0.1 | 3 | 2.44 ± 0.25 | 257 ± 74 | 1.0 ± 0.1 | 3 | 5.04 ± 0.66 | 299 ± 31 | 0.8 ± 0.0 | 3 |
| αβγV188C | 22.8 ± 6.0 | 1.4 ± 0.1 | 3 | 2.74 ± 0.17 | 253 ± 61 | 1.0 ± 0.0 | 3 | 4.75 ± 0.15 | 436 ± 46 | 0.8 ± 0.1 | 3 |
| αβγE189C | 16.6 ± 6.2 | 1.5 ± 0.1 | 4 | 1.48 ± 0.14** | 554 ± 108** | 0.9 ± 0.1 | 4 | 4.14 ± 0.63 | 679 ± 45** | 0.9 ± 0.1 | 4 |
| αβγV190C | 24.0 ± 3.4 | 1.6 ± 0.1 | 4 | 3.22 ± 0.31** | 434 ± 32** | 1.1 ± 0.2 | 3 | 4.22 ± 0.44 | 333 ± 32 | 0.9 ± 0.1 | 3 |
| αβγG191C | 11.1 ± 2.3** | 1.6 ± 0.2 | 4 | 3.83 ± 0.41** | 675 ± 120** | 1.1 ± 0.1 | 4 | 4.49 ± 0.25 | 439 ± 95 | 0.9 ± 0.1 | 3 |
| αβγD192C | 17.3 ± 3.5 | 1.5 ± 0.2 | 3 | 2.00 ± 0.25** | 282 ± 87 | 0.9 ± 0.1 | 4 | 3.85 ± 0.19 | 283 ± 59 | 0.9 ± 0.1 | 3 |
| αβγT193C | 23.7 ± 4.0 | 1.5 ± 0.2 | 3 | 2.67 ± 0.17 | 348 ± 55 | 1.0 ± 0.1 | 3 | 4.27 ± 0.06 | 309 ± 33 | 0.9 ± 0.0 | 3 |
| αβγR194C | 11.0 ± 4.2** | 1.4 ± 0.2 | 3 | 2.39 ± 0.24 | 238 ± 64 | 1.0 ± 0.2 | 6 | 3.12 ± 0.22* | 173 ± 46* | 1.0 ± 0.1 | 3 |
| αβγS195C | 29.6 ± 2.1 | 1.3 ± 0.1 | 3 | 2.02 ± 0.28** | 183 ± 78 | 1.1 ± 0.1 | 4 | 3.35 ± 0.53* | 192 ± 13* | 0.9 ± 0.0 | 3 |
| αβγW196C | 10.3 ± 2.1** | 1.1 ± 0.2 | 3 | 2.26 ± 0.12 | 357 ± 47 | 1.1 ± 0.2 | 5 | 4.37 ± 0.51 | 374 ± 37 | 0.8 ± 0.1 | 3 |
| αβγR197C | 17.4 ± 4.7 | 1.2 ± 0.1 | 4 | 0.64 ± 0.12** | 114 ± 43* | 1.2 ± 0.0 | 3 | 1.46 ± 0.20** | 92 ± 13** | 1.0 ± 0.1 | 3 |
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).