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.

ParameterPopulation Parameter EstimatePopulation Variance ModelPopulation SD(ω) or CORRbHypothesis TestsP Value (LRT)Interpretation
Agonist (5-HT)
 Min (µA)0 (fixed)
 Max (µA)4.94 ± 0.64× EXP(ɳ2)0.95 ± 0.10H0: ω2,2=0No resultaMax varies between oocytes
 COV(ɳ1,ɳ2)0.87 ± 0.05H0: ω1,2=04 × 10−9Max and pEC50 correlate strongly
 pEC505.65 ± 0.03+ ɳ10.18 ± 0.02H0: ω1,1=04 × 10−35pEC50 varies between oocytes
 nH2.94 ± 0.13H0: nH(A)=30.64Suggests three highly cooperative agonist binding sites
 nT−0.13 ± 0.06+ ɳ70.19 ± 0.06H0: nT=00.052Weak evidence for a change in response with time
H0: ω7=00.004nT varies between oocytes
Citral
 pIC503.92 ± 0.05+ ɳ50.16 ± 0.04H0: ω5=02 × 10−11pIC50 varies between oocytes
 nH1.34 ± 0.08H0: nH=15 × 10−6Indication of cooperative binding
 nG0 (fixed)H1: {nG,pA2,nS}≠00.94No evidence that citral changes agonist pEC50
Eucalyptol
 pIC503.59 ± 0.11+ ɳ40.32 ± 0.07H0: ω4=01 × 10−16pIC50 varies between oocytes
 nH1.04 ± 0.11H0: nH=10.76Suggests one inhibitor binding site
 nG1 (fixed)H0: nG=04 × 10−15Strong evidence that eucalyptol changes agonist pEC50
 pA23.09 ± 0.09+ ɳ30.18 ± 0.06H0: ω3=00.006pA2 varies between oocytes
 nS1.70 ± 0.24H0: nS=10.001Schild slope greater than that for competitive antagonism
Linalool
 pIC503.85 ± 0.02+ ɳ60.05 ± 0.02H0: ω6=00.023pIC50 varies between oocytes
 nH2.19 ± 0.26H0: nH=20.46Suggests two highly cooperative inhibitor binding sites
 nG0 (fixed)H1: {nG,pA2,nS}≠00.11No/weak evidence that linalool changes agonist pEC50
RUV model
 γ1.30 ± 0.07H0: γ=01 × 10−63Residual error variance increases with the current amplitude
 α0.30 ± 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.