Table 6.
IC50 values for inhibition of human α6/α3β4 mutants and α6/α3β2 nAChRs by α-Ctxs
Values in parentheses indicate the 95% CI of the data obtained from at least four oocytes per IC50 determination. The log(IC50 ratio) was calculated by dividing the IC50 value for each nAChR:α-Ctx combination (nAChR:PeIA analog, nAChR mutant:α-Ctx, or nAChR mutant:PeIA analog) by the IC50 for the WT:WT combination; negative values indicate higher potency, and positive values indicate lower potency. The -fold change in IC50 = nAChR:PeIA analog/WT:WT, nAChR mutant:α-Ctx/WT:WT, or nAChR mutant:PeIA analog/WT:WT. Note that for the latter comparison, the IC50 values are greater than the sum of each single nAChR mutant or PeIA analog combination (nAChR:PeIA analog/WT:WT or nAChR mutant:PeIA/WT:WT). Differences between IC50 values are considered substantial if ≥0.5 log units or ≥3-fold. WT, WT receptor or WT α-Ctx.
| nAChR:α-Ctx | IC50 | Log (IC50 ratio) | Change in IC50 | |
|---|---|---|---|---|
| nm | -fold | |||
| α6/α3β4:PeIA | 9.9 (8.2–11.9)a | |||
| α6/α3β4L119Q:PeIA | 94.3 (87.8–101)a | 1.0 | 10 | |
| α6/α3β4:[P13A]PeIA | 73.3 (66.8–80.5)a | 0.9 | 7 | |
| α6/α3β4L119Q:[P13A]PeIA | 244 (223–267) | 1.4 | 25 | |
| α6/α3β4:[P13R]PeIA | 188 (159–222)a | 1.3 | 19 | |
| α6/α3β4L119Q:[P13R]PeIA | 365 (331–403) | 1.6 | 37 | |
| α6/α3β4:[P13Q]PeIA | 34.0 (26.1–44.4)a | 0.5 | 3 | |
| α6/α3β4L119Q:[P13Q]PeIA | 363 (287–460) | 1.6 | 37 | |
| α6/α3β4L119F:PeIA | 13.0 (10.7–15.7)a | 0.1 | 1 | |
| α6/α3β4L119F:[P13A]PeIA | 56.7 (52.8–61.3) | 0.8 | 6 | |
| α6/α3β4L119F:[P13R]PeIA | 208 (170–256) | 1.3 | 21 | |
| α6/α3β2β3:PeIA | 16.0 (14.2–18.1)a | |||
| α6/α3β2β3:[P13A]PeIA | 30.6 (25.5–36.7) | 0.3 | 2 | |
| α6/α3β2β3:[P13R]PeIA | 8.9 (8.2–9.6) | −0.3 | 0.6 | |
| α6/α3β4:PnIA | 149 (135–164)a | |||
| α6/α3β4L119F:PnIA | 94.6 (87.9–102) | −0.2 | 0.6 | |
a Data previously shown for ease of comparison.