TABLE 1.
Output from the best fit model describing the effects of 5-HT and inhibitors on the peak current
The best fit was selected based the stability of convergence on the objective function (extended least squares = 110.89) and a comparison of Akaike information criteria (1,132.64) and Bayesian information criteria (1,226.72) values to alternative models. The model was further evaluated by examining the relationship between observed and predicted values, and population and individual residuals.
| Parameter |
Population Parameter Estimate |
Population Variance Model |
Population SD(ω) or CORRb | Hypothesis Tests |
P Value (LRT) |
Interpretation |
|---|---|---|---|---|---|---|
| Agonist (5-HT) | ||||||
| Min (µA) | 0 (fixed) | — | — | — | — | |
| Max (µA) | 4.94 ± 0.64 | × EXP(ɳ2) | 0.95 ± 0.10 | H0: ω2,2=0 | No resulta | Max varies between oocytes |
| COV(ɳ1,ɳ2) | 0.87 ± 0.05 | H0: ω1,2=0 | 4 × 10−9 | Max and pEC50 correlate strongly | ||
| pEC50 | 5.65 ± 0.03 | + ɳ1 | 0.18 ± 0.02 | H0: ω1,1=0 | 4 × 10−35 | pEC50 varies between oocytes |
| nH | 2.94 ± 0.13 | H0: nH(A)=3 | 0.64 | Suggests three highly cooperative agonist binding sites | ||
| nT | −0.13 ± 0.06 | + ɳ7 | 0.19 ± 0.06 | H0: nT=0 | 0.052 | Weak evidence for a change in response with time |
| H0: ω7=0 | 0.004 | nT varies between oocytes | ||||
| Citral | ||||||
| pIC50 | 3.92 ± 0.05 | + ɳ5 | 0.16 ± 0.04 | H0: ω5=0 | 2 × 10−11 | pIC50 varies between oocytes |
| nH | 1.34 ± 0.08 | H0: nH=1 | 5 × 10−6 | Indication of cooperative binding | ||
| nG | 0 (fixed) | H1: {nG,pA2,nS}≠0 | 0.94 | No evidence that citral changes agonist pEC50 | ||
| Eucalyptol | ||||||
| pIC50 | 3.59 ± 0.11 | + ɳ4 | 0.32 ± 0.07 | H0: ω4=0 | 1 × 10−16 | pIC50 varies between oocytes |
| nH | 1.04 ± 0.11 | H0: nH=1 | 0.76 | Suggests one inhibitor binding site | ||
| nG | 1 (fixed) | H0: nG=0 | 4 × 10−15 | Strong evidence that eucalyptol changes agonist pEC50 | ||
| pA2 | 3.09 ± 0.09 | + ɳ3 | 0.18 ± 0.06 | H0: ω3=0 | 0.006 | pA2 varies between oocytes |
| nS | 1.70 ± 0.24 | H0: nS=1 | 0.001 | Schild slope greater than that for competitive antagonism | ||
| Linalool | ||||||
| pIC50 | 3.85 ± 0.02 | + ɳ6 | 0.05 ± 0.02 | H0: ω6=0 | 0.023 | pIC50 varies between oocytes |
| nH | 2.19 ± 0.26 | H0: nH=2 | 0.46 | Suggests two highly cooperative inhibitor binding sites | ||
| nG | 0 (fixed) | H1: {nG,pA2,nS}≠0 | 0.11 | No/weak evidence that linalool changes agonist pEC50 | ||
| RUV model | ||||||
| γ | 1.30 ± 0.07 | H0: γ=0 | 1 × 10−63 | Residual error variance increases with the current amplitude | ||
| α | 0.30 ± 0.01 |
COV, covariance; LRT, likelihood ratio test.
a
No stable convergence was obtained without a random effect included.
b
Parameter estimates are shown ± standard errors.