Concentration–response data for ACh and NS3573 on wild-type, mutant, and concatenated α4β2 receptors expressed with different subunit ratios
| Subunits | Ratio | Imax (nA)a | ACh | NS3573 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EC50_1 (μm)b | EC50_2 (μm)b | Frac.c | nd | F value (DFn, DFd)e | EC50_1 (nm)b | EC50_2 (μm)b | Frac.c | nd | F value (DFn, DFd)e | |||
| α4:β2 | 1:4 | 920 | 1.6 | 6 | 23 | 20 | ||||||
| α4:β2 | 4:1 | 3800 | 0.95 | 83 | 0.16 | 17 | 38 (2,197) | 9.8 | 7.9 | 0.24 | 24 | 31 (2,279) |
| α4m:β2 | 1:4 | 360 | 0.97 | 7 | 20 | 7 | ||||||
| α4m:β2 | 4:1 | 1400 | 3.2 | 8 | 22 | 8 | ||||||
| α4m:β2 | 100:1 | 1500 | 3.8 | 9 | 27 | 10 | ||||||
| α4:β2m | 4:1 | 6600 | 140 | 7 | 23 | 11 | ||||||
| α4:β2 | 20:1 | 2900 | 1.4 | 141 | 0.14 | 20 | 58 (2,216) | 4.4 | 10 | 0.26 | 14 | 63 (2,131) |
| α4:β2 | 100:1 | 2700 | 1.9 | 170 | 0.15 | 24 | 80 (2,284) | 4.0 | 4.0 | 0.24 | 12 | 42 (2,138) |
| α4:β2-6-α4 | 1:1 | 2400 | 1.3 | 130 | 0.21 | 10 | 47 (2,116) | 6.3 | 6.3 | 0.23 | 5 | 12 (2,56) |
| α4:β2-6-α-9-β2-6-α4 | 1:1 | 3300 | 2.5 | 130 | 0.24 | 8 | 42 (2,80) | 5.0 | 7.9 | 0.26 | 9 | 64 (2,103) |
| β2-6-α-9-β2-6-α4:β2 | 1:1 | 290 | 1.3 | 12 | 18 | 13 | ||||||
↵aAverage of maximal ACh-evoked current amplitudes in X. laevis oocyte experiments. Oocytes were clamped at holding potentials ranging from −40 to −100 mV. Peak AChmax-evoked current amplitudes from each experiment were recorded and baseline subtracted. Average current levels for all experiments on a given receptor population were rounded off to two significant digits, and SEM values were typically 10%.
↵bEC50_1 and EC50_2 correspond to the high- and low sensitivity potencies observed from the wild-type α4β2 in a 4:1 ratio, respectively.
↵cFraction of the high-sensitivity component on receptors resulting in biphasic activation profiles.
↵dNumber of experiments behind the data.
↵eFor the experiments in which data were best fitted to biphasic Hill equations, the results from the best-model F test with p < 0.0001 are given as follows: F value (degrees of freedom for the numerator, degrees of freedom for the denominator).