TABLE 2 

Parameters for activation by propofol obtained by fitting concentration-response curves with predictions from the MWC model

The first column gives the concatemers expressed, whereas the second column gives the number of proposed propofol-binding sites mutated. The column headed L0 gives the ratio Pclosed/Popen for that receptor in the absence of added agonists. Data for L0 are given as arithmetic mean ± S.E.M. (95% confidence limits; number of observations). The Popen, const for wild-type βαγ-βα receptors would give an estimate of L0 = 8676 ± 1429 (n = 8). In other cases, L0 was estimated from the effect of picrotoxin on currents in the absence of other drugs. NP is the number of propofol-binding sites assumed in performing the fits (see Materials and Methods); for these values, it was assumed that the wild-type βαγ-βα receptor has NProp = 6. cP gives the ratio of the affinity of propofol to the open-channel to that for the closed-channel forms of the receptor. KP gives the affinity of propofol for the closed-channel form of the receptor. The values for cP and KP are given as best estimate for the parameter ± estimated S.E. provided by the fitting program (Origin v. 7.5).

Receptor#L0NPcPKP (µM)
βαγ-βα09000a60.22 ± 0.00321 ± 3
β(Y143W)αγ-βα13425 ± 680 (1539–5312; 5)50.20 ± 0.0039.0 ± 1.1
βαγ-β(Y143W)α12722 ± 540 (1223–4221; 5)50.22 ± 0.00413 ± 2
β(M286W)αγ-βα11457 ± 305 (672–2242; 6)b50.22 ± 0.00417 ± 3
βαγ-β(M286W)α117,083 ± 5940 (1813–32,354; 6)50.17 ± 0.00524 ± 6
β(Y143W)αγ-β(Y143W)α2141 ± 20 (85–198; 5)40.21 ± 0.0059.0 ± 0.9
β(Y143W+M286W)αγ-βα2155 ± 36 (69–241; 8)40.21 ± 0.00818 ± 3
βαγ-β(Y143W+M286W)α2123 ± 22 (68–177; 7)40.28 ± 0.01020 ± 5
β(M286W)αγ-β(M286W)α210,475 ± 1840 (6124–14,827; 8)b40.12 ± 0.00337 ± 8
β(Y143W+M286W)αγ-β(Y143W)α386 ± 19 (44–129; 10)30.17 ± 0.00713 ± 2
β(Y143W)αγ-β(Y143W+M286W)α313 ± 3 (6–20; 5)30.26 ± 0.01021 ± 2
β(Y143W+M286W)αγ-β(M286W)α367 ± 10 (41–94; 5)30.14 ± 0.01064 ± 12
β(M286W)αγ-β(Y143W+M286W)α3163 ± 27 (87–239; 5)30.24 ± 0.00524 ± 3
β(Y143W+M286W)αγ-β(Y143W+M286W)α413 ± 1 (12–15; 11)20.29 ± 0.02521 ± 8
  • a L0 set to value of 9000.

  • b Indicates L0 estimated from picrotoxin effect on a receptor additionally containing the α(L263S) mutation.