TABLE 1.
Parameters for agonist action at nAChR containing human or mouse α6 subunits
Potencies (micromolar EC50 values with 95% confidence intervals), Hill coefficients (nH ± S.E.), mean ± S.E. efficacies (Imax in nA), and concentrations where maximal peak current amplitudes (Imax) are achieved (in μm) are provided for the indicated agonist (ACh or nicotine) acting at nAChR composed of the indicated subunits derived from the specified species and from the indicated number of independent experiments (n) based on studies as shown in the figures. ↑ or ↓ indicates a significant (p < 0.05) increase or decrease, respectively, in potency or efficacy of the indicated agonist at the indicated nAChR subtype relative to nAChR containing the same subunits but in the absence of the indicated β3 subunit; ▴ or ▾ indicates a significant increase or decrease, respectively, in indicated agonist potency or efficacy at the indicated nAChR subtype relative to nAChR containing the same subunits in the presence wild-type β3 subunits, and △ or ▽ indicates a significant increase or decrease, respectively, in potency or efficacy of the indicated agonist at the indicated nAChR containing β3V13′S subunits relative to the same complex containing β3V9′S subunits. Note that no responses or very rare and then small responses were seen for the following subunit combinations (n = 9 each) to ACh or nicotine: hα6 + hβ2 alone or with hβ3 or hβ3V9′S or hβ3V13′S; and mα6 + mβ2 alone or with mβ3 or mβ3V9′S or mβ3V13′S. − indicates that absent or inconsistent functional responses in two-electrode voltage clamp studies precluded determination of the parameter of interest.
| Drug | nAChR subunit combinations | Potency |
Peak response |
||||
|---|---|---|---|---|---|---|---|
| n | EC50 (95% CI) | nH ± S.E. | n | Mean Imax ± S.E. | Imax concentration | ||
| μm | nA | μm | |||||
| ACh | hα6 + hβ4 | 9 | – | – | 3 | 22 ± 3 | 100 |
| hα6 + hβ4 + hβ3 | 9 | – | – | 9 | – | – | |
| hα6 + hβ4 + hβ3V9′S | 9 | 0.43 (0.34–0.54) ↑▴ | 0.69 ± 0.04 | 11 | 2100 ± 220 ↑▴ | 10 ↑▴ | |
| hα6 + hβ4 + hβ3V13′S | 3 | 1.2 (0.66–2.3) ↑ ▴ ▽ | 0.65 ± 0.10 | 3 | 910 ± 150 ↑▴ ▽ | 10 ↑▴ | |
| mα6 + mβ4 | 3 | 38 (25–58) | 0.72 ± 0.09 | 3 | 65 ± 25 | 1000 | |
| mα6 + mβ4 + mβ3 | 9 | – | – | 9 | – | – | |
| mα6 + mβ4 + mβ3V9′S | 4 | 0.42 (0.25–0.71) ↑▴ | 0.57 ± 0.08 | 3 | 2100 ± 190 ↑▴ | 100 ↑▴ | |
| mα6 + mβ4 + mβ3V13′S | 4 | 0.30 (0.22–0.41) ↑▴ | 0.71 ± 0.07 | 4 | 2400 ± 420 ↑▴ | 100 ↑▴ | |
| Nicotine | hα6 + hβ4 | 9 | – | – | 9 | – | – |
| hα6 + hβ4 + hβ3 | 9 | – | – | 9 | – | – | |
| hα6 + hβ4 + hβ3V9′S | 5 | 0.42 (0.26–0.68) ↑▴ | 0.70 ± 0.19 | 8 | 1900 ± 340 ↑▴ | 10 ↑▴ | |
| hα6 + hβ4 + hβ3V13′S | 4 | 0.30 (0.24–0.37) ↑▴ | 0.96 ± 0.08 | 4 | 1600 ± 54 ↑▴ | 10 ↑▴ | |
| mα6 + mβ4 | 3 | 26 (18–38) | 0.65 ± 0.13 | 5 | 27 ± 7 | 1000 | |
| mα6 + mβ4 + mβ3 | 9 | – | – | 9 | – | – | |
| mα6 + mβ4 + mβ3V9′S | 6 | 0.07 (0.04–0.10) ↑ ▴ | 0.89 ± 0.14 | 7 | 2500 ± 250 ↑▴ | 10 ↑▴ | |
| mα6 + mβ4 + mβ3V13′S | 4 | 0.26 (0.19–0.36) ↑▴ ▽ | 0.79 ± 0.08 | 4 | 3000 ± 360 ↑▴ | 10 ↑▴ | |