Data for the EC50 for propofol activation as a function of basal activity of the receptor for wild-type receptors or receptors containing mutations at locations outside of the putative propofol-binding sites
The first column gives the concatemers expressed, whereas the second column gives the background drug used to change the basal activity of the receptor. The column headed EC50 gives the EC50 for propofol activation determined for that level of basal activity, and L gives the ratio Pclosed/Popen for that receptor in the presence of the listed background drug. Data are given as arithmetic mean ± S.E.M. (95% confidence limits; number of observations). Note that bicuculline reduced the level of spontaneous current (thereby increasing L) as expected for an allosteric antagonist. In other cases, L was estimated from the basal activity in the absence of propofol.
| Receptor | Background Drug | EC50 | L |
|---|---|---|---|
| µM | |||
| βαγ-βα | None | 73 ± 6 (58–87; 9) | 9000 |
| βαγ-βα | 1 μM GABA | 11 ± 2 (5–16; 5) | 270 ± 74 (65–474; 5) |
| βαγ-βα | 10 μM GABA | 2.9 ± 0.4 (1.9–4.0; 5) | 6.4 ± 1.1 (3.4–9.4; 5) |
| βαγ-βα | 10 μM P4S | 4.7 ± 0.7 (2.7–6.7; 5) | 31 ± 12 (−2 to 65; 5) |
| βα(L263S)γ-βα(L263S) | None | 3.0 ± 0.2 (2.3–3.6; 5) | 7.3 ± 0.4 (6.3–8.3; 10)a |
| βα(L263S)γ-βα(L263S) | 0.1 μM GABA | 1.1 ± 0.1 (0.8–1.3; 5) | 3.5 ± 0.2 (3.0–4.0; 9) |
| βα(L263S)γ-βα(L263S) | 20 μM bicuculline | 6.5 ± 0.7 (4.5–8.6; 5) | 16 ± 1 (13–18; 5) |
| βαγ-β(Y205S)α | None | 68 ± 4 (56–80; 5) | 9000b |
| βαγ-β(Y205S)α | 20 μM GABA | 7.5 ± 0.6 (5.8–9.2; 5) | 204 ± 41 (90–318; 5) |
| βαγ-β(Y205S)α | 50 μM GABA | 7.1 ± 0.6 (5.4–8.8; 5) | 100 ± 10 (72–128; 5) |
| βαγ-β(Y205S)α | 100 μM GABA | 5.6 ± 0.4 (4.4–6.7; 5) | 47 ± 10 (20–74; 5) |
| βαγ-β(Y205S)α | 1000 μM GABA | 4.3 ± 1.0 (1.6–6.9; 5) | 39 ± 3 (31–47; 5) |