Table 2.
Half-maximum inhibitory concentration values (IC50).
| Drug | Stimulation frequency | WT hNav1.4 | F1586C | Y1593C |
||
|---|---|---|---|---|---|---|
| IC50 (μM) | IC50 (μM) | IC50 (μM) | Imax | |||
| Mexiletine | 0.1 Hz | 246 ± 15 | 1340 ± 72 | 476 ± 36 | 1 | |
| 10 Hz | 24.4 ± 1.8 | 1089 ± 181 | 169 ± 94 | 0.84 ± 0.17 | ||
| 0.1-to-10 Hz ratio | 10.1 | 1.2 | 2.8 | |||
| mHM | 0.1 Hz | 259 ± 28 | n.d. | n.d. | n.d. | |
| 10 Hz | 40.9 ± 4.7 | n.d. | n.d. | n.d. | ||
| 0.1-to-10 Hz ratio | 6.3 | n.d. | n.d. | |||
| pHM | 0.1 Hz | 1086 ± 183 | 1132 ± 36 | 908 ± 30 | 1 | |
| 10 Hz | 394 ± 82 | 847 ± 81 | 626 ± 45 | 0.74 ± 0.02 | ||
| 0.1-to-10 Hz ratio | 2.8 | 1.3 | 1.5 | HMM | ||
| 0.1 Hz | 2028 ± 255 | 2994 ± 74 | 1638 ± 14 | 1 | ||
| 10 Hz | 790 ± 91 | 2362 ± 187 | 1452 ± 111 | 0.76 ± 0.02 | ||
| 0.1-to-10 Hz ratio | 2.6 | 1.3 | 1.1 | bHMM | ||
| 0.1 Hz | 11883 ± 2992 | 28055 ± 10520 | 12740 ± 3141 | 1 | ||
| 10 Hz | 5190 ± 1021 | 17296 ± 2571 | 10353 ± 4102 | 0.78 ± 0.11 | ||
| 0.1-to-10 Hz ratio | 2.3 | 1.6 | 1.2 | pHHMM | ||
| 0.1 Hz | 30073 ± 7059 | 67730 ± 9125 | 24782 ± 2161 | 1 | ||
| 10 Hz | 13845 ± 2516 | 21056 ± 7650 | 13482 ± 1304 | 0.81 ± 0.03 | ||
| 0.1-to-10 Hz ratio | 2.2 | 3.2 | 1.8 | |||
These values were determined at the holding potential of −120 mV from the fit of concentration–response curves with the first-order bindingEq. 1described in Section “Materials and Methods.” The IC50 values are given together with SE of the fit. Regarding Y1593C, the Imax value was fixed to 1 at 0.1 Hz, but was variable at 10 Hz. n.d., Not determined.