Anesthetic-induced modulation of [3H]muscimol binding in wild-type and mutant GABAA receptors
| Subunit Combination | EC50 | Emax |
|---|---|---|
| μM | % control | |
| Pentobarbital | ||
| α1β2 | 23.40 ± 2.62 | 52.20 ± 5.69 |
| α1(G223F)β2 | 14.70 ± 2.141-a | 56.20 ± 6.55 |
| α1β2(G219F) | 9.60 ± 1.771-a | 21.20 ± 4.991-a 1-b |
| α1(G223F)β2(G219F) | 5.60 ± 1.211-a 1-b | 41.80 ± 4.97 |
| ρ1 | NR1-g | NR1-g |
| ρ1(F261G) | 306.30 ± 49.701-a 1-e 1-f | −29.80 ± 6.511-a 1-e 1-f |
| ρ1(NASM-RNSL) | NR1-g | NR1-g |
| Alphaxalone | ||
| α1β2 | 0.44 ± 0.07 | 60.80 ± 4.13 |
| α1(G223F)β2 | 0.17 ± 0.031-a | 71.80 ± 9.47 |
| α1β2(G219F) | 0.12 ± 0.031-a | −11.80 ± 1.491-a 1-b 1-d |
| α1(G223F)β2(G219F) | 0.08 ± 0.031-a | 35.50 ± 3.931-a 1-b |
| ρ1 | NR1-g | NR1-g |
| ρ1(F261G) | 0.27 ± 0.11 | −28.00 ± 3.701-a 1-b 1-d 1-e |
| ρ1(NASM-RNSL) | 0.70 ± 0.191-e | −15.0 ± 3.161-a 1-b 1-d |
| Etomidate | ||
| α1β2 | 1.83 ± 0.13 | 300.30 ± 39.40 |
| α1(G223F)β2 | 0.48 ± 0.041-a 1-c | 117.70 ± 6.171-a |
| α1β2(G219F) | 2.92 ± 0.56 | 19.70 ± 5.701-a 1-b |
| α1(G223F)β2(G219F) | 0.94 ± 0.201-a 1-c | 59.30 ± 0.881-a |
| ρ1 | NR1-g | NR1-g |
| ρ1(F261G) | 0.40 ± 0.151-a 1-c | 19.70 ± 1.451-a 1-b 1-e 1-f |
| ρ1(NASM-RNSL) | NR1-g | NR1-g |
| Propofol | ||
| α1β2 | 6.20 ± 0.85 | 166.30 ± 16.33 |
| α1(G223F)β2 | 4.09 ± 0.991-d | 77.30 ± 1.201-a |
| α1β2(G219F) | 1.61 ± 0.471-a 1-d | 35.30 ± 5.041-a 1-b |
| α1(G223F)β2(G219F) | 8.06 ± 1.00 | 17.30 ± 4.481-a 1-b |
| ρ1 | NR1-g | NR1-g |
| ρ1(F261G) | 6.70 ± 0.49 | 21.30 ± 7.311-a 1-b |
| ρ1(NASM-RNSL) | NR1-g | NR1-g |
From the curve fit of concentration-response data, values (n = 3–4 experiments performed in triplicate, mean ± S.E.) indicate the EC50 andE max for modulation by each i.v. anesthetic. Control values were evaluated in the absence of anesthetic.
↵1-a P < .05 compared with α1β2.
↵1-b P < .05 compared with α1(G223F)β2.
↵1-c P < .05 compared with α1β2(G219F).
↵1-d P < .05 compared with α1(G223F)β2(G219F).
↵1-e P < .05 compared with ρ1.
↵1-f P < .05 compared with ρ1(NASM-RNSL).
↵1-g NR, tested with no statistically significant response,P > .05.