Table 2.
Functional and Pharmacological Characteristics of α1β3γ2L GABAA Receptors with β3 Cysteine Substitutions
| Receptor Type | GABA EC50(μM) [95% CI] (n) | GABA Efficacy mean ± se (n) | Spont. Activation mean ± se (n) | Maximal Effect of pCMBS Modification (range) |
|---|---|---|---|---|
| α1β3γ2L | 31 [23 to 41] (8) | 0.88 ± 0.025 (5) | < 0.005 (5) | No effect |
| α1β3T262Cγ2L | 21 [18 to 25] (4) | 0.93 ± 0.03 (4) | < 0.005 (3) | Reduce max current (95–99%) |
| α1β3T266Cγ2L | 143 [130 to 157] (6) *** | 0.88 + 0.02 (4) | < 0.005 (3) | ↑ lo/hi GABA response (10 to 13-fold) |
| α1β3M283Cγ2L | 46 [43 to 50] (3) | 0.92 ± 0.023 (3) | < 0.005 (3) | No effect |
| α1β3M286Cγ2L | 148 [122 to 180] (3) *** | 0.65 ± 0.023 (3) ** | < 0.005 (3) | ↑ lo/hi GABA response (5.8 to 7.8-fold) |
| α1β3G287Cγ2L | 78 [67 to 92] (4) ** | 0.96 ± 0.034 (4) * | < 0.005 (3) | ↑ lo/hi GABA response (2.3 to 3.5-fold) |
| α1β3F289Cγ2L | 5.9 [5.3 to 6.7] (4) *** | 0.99 ± 0.02 (4) ** | 0.034 ± 0.016* (4) | ↑ lo/hi GABA response (2.8 to 4.0-fold) |
| α1β3V290Cγ2L | 36 [32 to 41] (4) | 0.92 ± 0.03 (4) | < 0.005 (3) | ↑ lo/hi GABA response (2.3 to 3.1-fold) |
| α1β3F293Cγ2L | 181 [143 to 229] (3) *** | 0.16 ± 0.018 (3) *** | < 0.005 (3) | ↑ lo/hi GABA response (2.6 to 4.3-fold) |
| α1β3L297Cγ2L | 114 [104 to 125] (4) *** | 0.54 ± 0.07 (5) *** | < 0.005 (4) | ↑ lo/hi GABA response (5.5 to 7.2-fold) |
| α1β3E298Cγ2L | 103 [88 to 112] (4) *** | 0.63 ± 0.07 (3) *** | < 0.005 (3) | ↑ lo/hi GABA response (3.5 to 5.5-fold) |
| α1β3F301Cγ2L | 34 [30 to 39] (4) | 0.93 ± 0.04 (4) | < 0.005 (4) | ↑ lo/hi GABA response (3.8 to 4.9-fold) |
Differs from wild-type at:
*
p < 0.0045,
**
p < 0.0005,
***
p < 0.0001