Table 1.
Parameters for drug action at human α2*-nAChR
| Potency |
Peak Response |
|||||||
|---|---|---|---|---|---|---|---|---|
| Agonist | nAChR subunit combinations | n | EC50 (μM) (95% CI) | nH ± SE nH | n | Imax (nA) (mean ± SE) | τ (ms) | Imax conc. (μM) |
| ACh | α2β2 | 5 | 59 (45–77) | 1.02 ± 0.13 | 5 | 25 ± 3 | 5400 ± 400 | 1000 |
| α2β2β3 | 3 | 48 (38–60) | 1.11 ± 0.12 | 3 | 25 ± 3 | 4500 ± 800 | 1000 | |
| α2β2β3V9'S | 9 | 0.89 (0.69–1.16)↑▲ | 0.65 ± 0.05 | 12 | 38 ± 4 ↑▲ | 6200 ± 900 | 100↑▲ | |
| α2β4 | 5 | 18 (17–19) | 1.33 ± 0.06 | 4 | 3800 ± 800 | 1600 ± 300 | 316 | |
| α2β4β3 | 4 | 20 (19–20)↓ | 1.39 ± 0.03 | 3 | 2500 ± 200 | 1500 ± 200 | 316 | |
| α2β4β3V9'S | 4 | 4.8 (4.2–5.5)↑▲ | 0.99 ± 0.06 | 4 | 6300 ± 600↑▲ | 2800 ± 600 | 316 | |
| Nicotine | α2β2 | 5 | 10 (8–13) | 0.99 ± 0.13 | 5 | 30 ± 2 | 7900 ± 2500 | 100 |
| α2β2β3 | 4 | 12 (9–15) | 1.08 ± 0.14 | 5 | 20 ± 3↓ | 3200 ± 700 | 100 | |
| α2β2β3V9'S | 4 | 1.1 (0.9–1.3)↑▲ | 1.08 ± 0.11 | 4 | 78 ± 13↑▲ | 1700 ± 300↓ | 10↑▲ | |
| α2β4 | 4 | 8.6 (7.5–9.8) | 1.34 ± 0.11 | 4 | 3500 ± 900 | – | 100 | |
| α2β4β3 | 4 | 7.3 (6.5–8.1) | 1.28 ± 0.08 | 4 | 2200 ± 700 | 2400 ± 700 | 100 | |
| α2β4β3V9'S | 4 | 2.0 (1.6–2.5)↑▲ | 1.06 ± 0.12 | 3 | 5500 ± 900↑▲ | 3900 ± 300 | 100 | |
Potencies (micromolar EC50 values and 95% confidence intervals), Hill coefficents (nH ± SE), mean ± SE peak current responses (Imax in nanoamps), current desensitization time constants (τ ± SE in milliseconds), and the concentration where Imax is achieved (μM) are provided for the indicated agonist (ACh or nicotine) acting at nAChR composed of the indicated subunits and from the indicated number of independent experiments based on studies as shown in Fig. 1 and Figure S1. ↑ or ↓ indicate a significant (p < 0.05) increase or decrease, respectively, in the relevant parameter at the indicated nAChR subtype relative to nAChR containing the same subunits but in the absence of the indicated β3 subunit; and ▲ indicates a significant increase, in the relevant parameter of the indicated nAChR subtype relative to nAChR containing the same subunits in the presence wild-type β3 subunits. ‘–’ indicates cases where negligible desensitization was evident, precluding accuracy in fits of the data to mono- or bi-phasic current decay models.