Table 3.
Comparison of IC50 and Ki values (nM) for DHβE blockade of ACh-stimulated DA release
| Genotype | IC50 (nM) α4β2-mediated α-CtxMII- resistant using 3 µM ACh |
IC50 (nM) α4β2-mediated α-CtxMII- resistant using 0.3 µM ACh |
IC50 (nM) α6β2-mediated α-CtxMII- sensitive using 3 µM ACh |
IC50 (nM) α6β2-mediated α-CtxMII- sensitive using 0.3 µM ACh |
|---|---|---|---|---|
| +/+ | 60 ± 4 | 11 ± 1 | 1848 ± 848 | 238 ± 169 |
| +/Leu9’Ala | 95 ± 23 | 12 ± 4 | 1175 ± 358 | 180 ± 49 |
| Leu9’Ala/Leu9’Ala | 1175 ± 412 *+ | 68 ± 12 *+ | 714 ± 140 | 118 ± 35 |
| Ki (nM) α4β2-mediated α-CtxMII- resistant using 3 µM ACh |
Ki (nM) α4β2-mediated α-CtxMII- resistant using 0.3 µM ACh |
Ki (nM) α6β2-mediated α-CtxMII- sensitive using 3 µM ACh |
Ki (nM) α6β2-mediated α-CtxMII- sensitive using 0.3 µM ACh |
|
| +/+ | 12 ± 1 | 8 ± 1 | 83 ± 38 | 77 ± 55 |
| +/Leu9’Ala | 9 ± 2 | 6 ± 2 | 42 ± 13 | 49 ± 13 |
| Leu9Ala/Leu9Ala | 31 ± 11 *+ | 14 ± 3 *+ | 53 ± 10 | 39 ± 12 |
significantly different from +/+.
significantly different from +/Leu9′Ala.
Notes: Data collected at 3 µM ACh from 5 WT, 4 HET, 2 HOM mice and at 0.3 uM ACh from 5 WT, 4 HET, 3 HOM mice. For each, 4–5 concentrations of DHβE were assayed, 0, 0.01, 0.1, 1, 10 µM with and without 50 nM αCtxMII. Data was curve fit from all individual points for each ACh concentration using the single exponential decay equation: f=a*exp(-b*x), where a=uninhibited release, b=decay constant and 0.693/b=IC50 value. The Ki values were calculated from the equation: Ki=IC50/(1+[ACh]/EC50) where EC50 values are taken from Table 1. By ANOVA, using all determinations of Ki, the resistant Ki for mutant is significantly different than WT.