Activation of wild-type and mutated receptors by propofol
The first column (“Receptor”) gives the concatemers expressed, whereas the second column (#) gives the number of putative propofol-binding sites mutated. The third and fourth columns give the probability of being open in the absence of GABAergic drugs (Popen, const) and in the presence of saturating propofol (Popen, max). The columns headed EC50 and nH give parameters from fitting concentration-response curves for activation by propofol. Data are given as arithmetic mean ± S.E.M. (95% confidence limits; number of observations).
| Receptor | # | Popen, const | Popen, max | EC50 | nH |
|---|---|---|---|---|---|
| µM | |||||
| βαγ-βα | 0 | 0.00015 ± 0.00003 (0.00009–0.00020; 8) | 0.48 ± 0.03 (0.38–0.57; 5) | 73 ± 6 (58–87; 9) | 2.8 ± 0.2 (2.4–3.2; 9) |
| β(Y143W)αγ-βα | 1 | 0.00033 ± 0.00006 (0.00018–0.00049; 5) | 0.41 ± 0.02 (0.36–0.45; 6) | 23 ± 1 (19–27; 5) | 2.3 ± 0.1 (2.0–2.5; 5) |
| βαγ-β(Y143W)α | 1 | 0.00048 ± 0.00015 (0.00006–0.00090; 5) | 0.36 ± 0.06 (0.17–0.55; 4) | 35 ± 4 (23–48; 5) | 2.1 ± 0.1 (1.9–2.4; 5) |
| β(M286W)αγ-βα | 1 | ND | 0.52 ± 0.05 (0.41–0.63; 8) | 44 ± 2 (38–50; 5) | 2.3 ± 0.1 (2.0–2.6; 5) |
| βαγ-β(M286W)α | 1 | ND | 0.22 ± 0.02 (0.16–0.27; 7) | 79 ± 6 (64–93; 6) | 3.1 ± 0.2 (2.6–3.5; 6) |
| β(Y143W)αγ-β(Y143W)α | 2 | 0.0077 ± 0.0012 (0.0043–0.0111; 5) | 0.75 ± 0.03 (0.67–0.83; 5) | 12 ± 1 (9–14; 6) | 1.6 ± 0.1 (1.2–2.0; 6) |
| β(Y143W+M286W)αγ-βα | 2 | 0.0096 ± 0.0023 (0.0042–0.0150; 8) | 0.71 ± 0.06 (0.59–0.84; 9) | 22 ± 4 (12–32; 5) | 2.6 ± 0.5 (1.3–3.9; 5) |
| βαγ-β(Y143W+M286W)α | 2 | 0.010 ± 0.002 (0.005–0.016; 7) | 0.51 ± 0.04 (0.41–0.60; 7) | 29 ± 2 (24–33; 5) | 2.5 ± 0.2 (2.0–3.0; 5) |
| β(M286W)αγ-β(M286W)α | 2 | ND | 0.25 ± 0.05 (0.14–0.36; 8) | 107 ± 7 (89–125; 5) | 2.9 ± 0.4 (1.9–3.9; 5) |
| β(Y143W+M286W)αγ-β(Y143W)α | 3 | 0.019 ± 0.005 (0.008–0.030; 10) | 0.63 ± 0.06 (0.49–0.77; 7) | 12 ± 1 (9–15; 5) | 2.2 ± 0.0 (2.0–2.3; 5) |
| β(Y143W)αγ-β(Y143W+M286W)α | 3 | 0.081 ± 0.016 (0.037–0.125; 5) | 0.79 ± 0.03 (0.69–0.89; 5) | 15 ± 1 (12–18; 6) | 1.4 ± 0.1 (1.1–1.7; 6) |
| β(Y143W+M286W)αγ-β(M286W)α | 3 | 0.016 ± 0.002 (0.010–0.022; 5) | 0.77 ± 0.03 (0.69–0.85; 5) | 43 ± 4 (33–54; 6) | 2.2 ± 0.1 (1.9–2.6; 6) |
| β(M286W)αγ-β(Y143W+M286W)α | 3 | 0.0071 ± 0.0015 (0.0029–0.0113; 5) | 0.27 ± 0.02 (0.22–0.31; 5) | 43 ± 4 (33–53; 5) | 1.6 ± 0.0 (1.6–1.7; 5) |
| β(Y143W+M286W)αγ-β(Y143W+M286W)α | 4 | 0.057 ± 0.013 (0.028–0.086; 12) | 0.47 ± 0.05 (0.34–0.60; 6) | 13 ± 0 (12–14; 7) | 2.0 ± 0.3 (1.3–2.7; 7) |
ND, picrotoxin had no effect on holding current