Affinities of different DHPs for recombinant Cav1.3 and Cav1.2 channels
Ligand concentration was 0.13 to 0.15 nM. Membrane protein concentration was 40 to 100 μg/ml. Data are given as means ± S.D. for n = 5. Statistical significance of selectivity was obtained as described in Table 2. Selectivity ratios (WT:MUT) were calculated from individual experiments carried out in parallel for both channel isoforms.
Dihydropyridine | Cav1.2 | Cav1.3 | IC50 WT:MUT |
|---|---|---|---|
| (±)-Isradipine | |||
| IC50 (nM) | 0.40 ± 0.21 | 0.51 ± 0.20 | 0.76 ± 0.18* |
| Slope factor | 0.80 ± 0.04 | 0.96 ± 0.12 | |
| Azidopine | |||
| IC50 (nM) | 0.46 ± 0.10 | 0.65 ± 0.11+ | 0.74 ± 0.23 |
| Slope factor | 0.85 ± 0.06 | 1.00 ± 0.11 | |
| Nitrendipine | |||
| IC50 (nM) | 1.08 ± 0.27 | 3.59 ± 0.66+++ | 0.31 ± 0.11*** |
| Slope factor | 0.82 ± 0.10 | 0.96 ± 0.12 | |
| Nifedipine | |||
| IC50 (nM) | 4.45 ± 1.21 | 20.1 ± 4.78+++ | 0.22 ± 0.04*** |
| Slope factor | 0.84 ± 0.12 | 0.92 ± 0.10 | |
| (−)-Isradipine | |||
| IC50 (nM) | 29.7 ± 5.56 | 27.2 ± 3.67 | 1.09 ± 0.11 |
| Slope factor | 0.88 ± 0.13 | 0.86 ± 0.12 | |
| Amlodipine | |||
| IC50 (nM) | 28.4 ± 11.8 | 60.1 ± 28.3 | 0.48 ± 0.11*** |
| Slope factor | 0.87 ± 0.11 | 0.94 ± 0.09 |
|