Table 2. Regression results from fitted zolpidem responses at wild-type and concatenated GABAARs.
Zolpidem | |||||
---|---|---|---|---|---|
Construct | Subunit | EC50 (µM) | pEC50 | n | GABA316 µM (nA) |
α1 + β2 1:50 | No effect | 7 | 2,100 ± 300 | ||
α1 + β2 50:1 | No effect | 6 | 750 ± 250 | ||
α1 + β2 + γ2 5:1:5 | 0.11 | 6.95 ± 0.02 | 11 | 2,900 ± 500 | |
Dimeric constructs | |||||
β2-23-α1 | γ2 | 0.10 | 7.00 ± 0.03 | 8 | 7,600 ± 700 |
α1-10-β2 | γ2 | 0.18 | 6.74 ± 0.03 | 7 | 14,000 ± 6,000 |
α1-9a-β2 | γ2 | 0.19 | 6.72 ± 0.03 | 14 | 7,000 ± 1,000 |
α1-6a-β2 | γ2 | 0.15 | 6.83 ± 0.03 | 8 | 4,000 ± 500 |
α1-3a-β2 | γ2 | 0.20 | 6.71 ± 0.04 | 7 | 5,600 ± 1,300 |
α1-0a-β2 | γ2 | 0.21 | 6.68 ± 0.03 | 12 | 280 ± 50 |
Tetrameric constructs | |||||
α1-10-β2-α1-β2 | γ2 | 0.10 | 7.00 ± 0.03 | 9 | 5,000 ± 500 |
α1-10-β2-α1-γ2 | β2 | 0.092 | 7.04 ± 0.02 | 7 | 5,800 ± 400 |
Pentameric constructs | |||||
α1-(-1a)-β2-α1-β2-γ2 | 0.17 | 6.76 ± 0.02 | 6 | 150 ± 50a | |
α1-(-1a)-β2-α1-γ2-β2 | 0.19 | 6.72 ± 0.02 | 12 | 2,300 ± 300a | |
γ2-15a-β2-α1-β2-α1 | 0.15 | 6.82 ± 0.02 | 9 | 6,100 ± 1,200 | |
γ2-13a-β2-α1-β2-α1 | 0.22 | 6.65 ± 0.02 | 11 | 4,400 ± 600a | |
γ2-11a-β2-α1-β2-α1 | 0.27 | 6.57 ± 0.03 | 12 | 2,000 ± 30a | |
γ2-10a-β2-α1-β2-α1 | 0.14 | 6.86 ± 0.02 | 11 | 1,700 ± 200a | |
γ2-9a-β2-α1-β2-α1 | 0.17 | 6.78 ± 0.03 | 14 | 800 ± 150a | |
Mutant constructs | |||||
α1-9a-β2 | γ2(A118R) | 3.4 | 5.46 ± 0.04 | 11 | 8,600 ± 1,100 |
α1-0a-β2 | γ2(A118R) | 2.0 | 5.70 ± 0.03 | 7 | 990 ± 90 |
α1R94A + β2 + γ2 5:1:5 | 0.20 | 6.71 ± 0.02 | 7 | 990 ± 110a | |
γ2-11a-β2-α1-β2-α1R94A | 0.36 | 6.44 ± 0.03 | 11 | 350 ± 50a | |
γ2-11a-β2-α1-β2-α1R94A | α1 | 0.20 | 6.71 ± 0.03 | 9 | 510 ± 130a |
Data points were fitted to the Hill equation with bottom set to 0 and Hill slope set to 1 by nonlinear regression. Fitted potencies of zolpidem are presented as EC50 in µM and pEC50 ± SEM where p = −Log for the indicated number (n) of individual oocytes. The average peak-current amplitudes obtained with GABA316 µM applications are presented as mean ± SEM in nA for the tested oocytes. No effect, no positive enhancement of GABAcontrol-evoked currents was observed.
Due to the GABA EC50 value on this receptor, GABA316 µM applications do not represent a maximal EC100 concentration.