Estimated IC50 values for block of hNav1.5 wild-type and mutant NaChs by prenylamine and bupivacaine
| Hyperpolarized State IC50 | Ratio Mutant/Wild-type | Depolarized State IC50 | Ratio Mutant/Wild-type | |
|---|---|---|---|---|
| μM | μM | |||
| Bupivacaine | ||||
| Wild-type | 177.8 | 2.6 | ||
| F1760K | 809.1 | 4.5 | 179.0 | 68.5 |
| Prenylamine | ||||
| Wild-type | 9.7 | 0.7 | ||
| F1760K | 16.5 | 1.7 | 2.9 | 4.0 |
| N1765K | 16.4 | 1.7 | 1.6 | 2.2 |
| Y1767K | 14.2 | 1.5 | 1.5 | 2.1 |
| I1466K | 13.6 | 1.4 | 0.6 | 0.8 |
| N406K | 14.6 | 1.5 | 4.2 | 5.8 |
| L409K | 16.9 | 1.7 | 4.2 | 5.8 |
| N927K | 8.9 | 0.9 | 0.9 | 1.3 |
| L931K | 13.6 | 1.4 | 2.3 | 3.2 |
The IC50 values for prenylamine block of wild-type channels were derived from concentration-inhibition experiments at both the hyperpolarized state (−180 mV) and depolarized state (−70 mV). The IC50 values for prenylamine block of mutant channels and bupivacaine block of channels were estimated by the formula Y= Y max / [1 + (X / IC50)n H , whereY is the current remaining, Y max is the maximum current without drug, X is the drug concentration (3 μM to 100 μM), and n H is the Hill coefficient.