Table 2.
NS9283 promotes ACh-elicited channel re-opening
| Receptor type (number of patches) | [ACh] μM | [NS9283] μM | Best model (p < 0.01) | Mean re-opening (95% IC) [% phase (95% IC)] | Significance (p < 0.01) | |||
|---|---|---|---|---|---|---|---|---|
| First phase | Second phase | First phase | Second phase | % First phase | ||||
| (α4)3(β2)2 (n = 6) | 50 | 30 | Biphasic |
2 (1.9–2.2) [59 (56–62)] |
10 (9.6–10.6) [41 (38–44)] |
Yes | Yes | Yes |
| (α4)3(β2)2 (n = 4) | 50 | Biphasic |
0.7 (0.69–0.73) [71 (69–72)] |
2.8 (2.7–2.9) [29 (28–31)] |
||||
| (α4)3(β2W176A)2 (n = 6) | 50 | 30 | Biphasic |
0.57 (0.5–0.6) [60 (56–64)] |
2.2 (2.0–2.3) [40 (36–44)] |
Yes | n.d. | n.d. |
| (α4)3(β2W176A)2 (n = 4) | 50 | One phase |
0.63 (0.57–0.71) [1] |
|||||
| (α4H142V)3(β2)2 (n = 17) | 50 | 30 | Biphasic |
0.58 (0.5–0.6) [75 (66–81)] |
2.6 (2.0–3.6) [25 (19–34)] |
No | No | No |
| (α4H142V)3(β2)2 (n = 4) | 50 | Biphasic |
0.58 (0.56–0.6) [75 (72–78)] |
1.6 (1.5–1.7) [25 (22–28)] |
||||
| β2α4β2α4α4 (n = 6) | 50 | 30 | Biphasic |
1.7 (1.5–1.9) [37 (34–40)] |
7.7 (7.4–8.0) [63 (60–66)] |
Yes | Yes | Yes |
| β2α4β2α4α4 (n = 5) | 50 | Biphasic |
0.5 (0.4–0.6) [47 (43–52)] |
2.7 (2.5–2.8) [53 (48–57)] |
||||
| β2W176Aα4β2α4α4 (n = 6) | 50 | 30 | Biphasic |
1.3 (1.2–1.4) [70 (64–75)] |
3.9 (3.5–4.4) [30 (25–36)] |
Yes | Yes | No |
| β2W176Aα4β2α4α4 (n = 4) | 50 | Biphasic |
0.4 (0.2–0.5) [67 (46–82)] |
1.6 (1.2–2.4) [33 (18–54)] |
||||
| β2α4β2W176Aα4α4 (n = 8) | 50 | 30 | Biphasic |
0.58 (0.52–0.64) [63 (58–68)] |
2.9 (2.5–3.2) [37 (32–42)] |
No | No | Yes |
| β2α4β2W176Aα4α4 (n = 6) | 50 | Biphasic |
0.5 (0.45–0.57) [77 (72–82)] |
3 (2.5–3.7) [23 (18–28)] |
||||
| β2W176Aα4β2W176Aα4α4 (n = 10) | 50 | 30 | Biphasic |
0.55 (0.5–0.6) [65 (60–70)] |
2.3 (2.1–2.5) [35 (30–40)] |
No | n.d. | n.d. |
| β2W176Aα4β2W176Aα4α4 (n = 7) | 50 | One phase |
0.76 (0.4–1.2) [1] |
|||||
| β2α4β2α4H142Vα4 (n = 8) | 50 | 30 | Biphasic |
1.2 (1.0–1.3) [63 (57–69)] |
5.4 (4.7–6.2) [37 (43–31)] |
Yes | Yes | No |
| β2α4β2α4H142Vα4 (n = 9) | 50 | Biphasic |
0.5 (0.4–0.6) [62 (56–68)] |
2.2 (1.9–2.4) [38 (32–44)] |
||||
Mean number of re-openings and the relative percentage of the corresponding phase are given along with the 95% confidence interval (95% IC). An F test was used to determine whether a monophasic or biphasic model best described the data, and to determine whether the fitted decay rates and fractional areas differed significantly without versus with NS9283. The table summarizes results displayed in Fig. 5