TABLE 1.
Pharmacological, kinetic, and Monod-Wyman-Changeux (MWC) coagonist model parameters for α1β2γ2L and α1β2M286Cγ2L GABAA receptors
| Parameter | α1β2γ2L | α1β2M286Cγ2L |
|---|---|---|
| Mean ± S.D. (n)a | Mean ± S.D. (n) | |
| GABA EC50 (μM) | 37 ± 17 (7) | 210 ± 35 (6)** |
| nH | 1.6 ± 0.39 (7) | 1.5 ± 0.33 (6) |
| GABA efficacy (%)b | 88 ± 5 (4) | 64 ± 4.2 (4)** |
| GABA EC50 shift with 3.2 μM etomidatec | 19 ± 7.8 (7) | 2.7 ± 0.75 (4)** |
| Etomidate EC50 (μM) | 30 ± 11 (6) | Na |
| Etomidate efficacy (%) | 45 ± 12 (6) | < 1 (4)** |
| Maximal activation | ||
| Rate (s−1) | 3000 ± 1200 (4) | 2500 ± 940 (4) |
| Fast desensitization | ||
| Rate (s−1) | 20 ± 13 | 16 ± 9.4 |
| Amplitude (%) | 30 ± 11 (4) | 30 ± 18 (4) |
| Slow desensitization | ||
| Rate (s−1) | 1.0 ± 0.45 | 0.8 ± 0.29 |
| Amplitude (%)) | 70 ± 11 (4) | 70 ± 17 (4) |
| Fast deactivation | ||
| Rate (s−1) | 50 ± 18 | 57 ± 27 |
| Amplitude (%) | 60 ± 17 (4) | 70 ± 17 (4) |
| Slow deactivation | ||
| Rate (s−1) | 6 ± 2.5 | 4 ± 2.7 |
| Amplitude (%) | 40 ± 17 (4) | 30 ± 17 (4) |
| L0d | 25,000 | 75,000 |
| KG (μM) | 70 ± 22 | 270 ± 46** |
| c | (1.9 ± 0.38) × 10−3 | (2.4 ± 0.15) × 10−3 |
| KE (μM) | 40 ± 14 | 12 ± 2.4* |
| d | (7.6 ± 1.0) × 10−3 | 0.12 ± 0.018** |
n is the number of separately analyzed experiments in individual oocytes, patches or cells used to calculate averages and errors. Average values for wild-type include previously published data from Stewart et al. (2008) and Desai et al. (2009).
GABA efficacy was determined as the ratio of maximal GABA current to current elicited with maximal GABA + 2 μM alphaxalone.
EC50 shift is the ratio of GABA EC50 in the absence versus presence of 3.2 μM etomidate. Large values indicate significant positive modulation. A value of 1.0 represents no modulation.
MWC model parameters (L0, KG, KE, c, d) were derived from fits of eq. 3 to estimated Popen values (see Materials and Methods and Fig. 2).
P < 0.05; ** P < 0.01.