Table 1.
Half inactivation voltage (V1/2) and use-dependence of inhibition for the Nav1.7 mutations to lacosamide
| Variant | Slow inactivation (V1/2) | Fast inactivation (V1/2) | Use-dependence | |||
|---|---|---|---|---|---|---|
| Vehicle | Lacosamide | Vehicle | Lacosamide | Vehicle | Lacosamide | |
| Wild-type | −70.6 ± 1.4 (n = 16) | −79.5 ± 2.1** (n = 9) | −86.8 ± 1.4 (n = 19) | −88.0 ± 1.9 (n = 8) | 0.82 ± 0.02 (n = 20) | 0.75 ± 0.02* (n = 9) |
| Responders | ||||||
| W719C | −56.9 ± 4.4 (n = 8) | −77.1 ± 5.3* (n = 4) | −78.7 ± 0.8 (n = 11) | −88.4 ± 1.3** (n = 5) | 0.96 ± 0.01 (n = 10) | 0.87 ± 0.04** (n = 4) |
| I739V | −67.1 ± 1.6 (n = 12) | −79.3 ± 2.1** (n = 5) | −85.2 ± 1.0 (n = 11) | −99.8 ± 1.1** (n = 6) | 0.82 ± 0.01 (n = 16) | 0.73 ± 0.03** (n = 5) |
| Non-responders | ||||||
| L1267V | −74.4 ± 2.1 (n = 9) | −83.7 ± 2.7* (n = 8) | −82.5 ± 2.4 (n = 7) | −87.1 ± 1.6 (n = 11) | 0.89 ± 0.02 (n = 12) | 0.87 ± 0.02 (n = 10) |
| W1538R | −69.4 ± 4.0 (n = 10) | −68.0 ± 2.8 (n = 8) | −79.5 ± 3.0 (n = 10) | −73.9 ± 1.2 (n = 8) | 0.91 ± 0.02 (n = 11) | 0.93 ± 0.01 (n = 8) |
| I228M | −66.0 ± 2.9 (n = 7) | −78.1 ± 2.5** (n = 7) | −87.1 ± 1.6 (n = 11) | −88.9 ± 2.8 (n = 6) | 0.82 ± 0.03 (n = 6) | 0.75 ± 0.01* (n = 7) |
Lacosamide significantly enhanced slow inactivation in wild-type and all mutant channels, except for W1538R, while fast inactivation was only affected by lacosamide in W719C and I739V channels. Use-dependence of inhibition at 20 Hz was changed in the two responder variants as well as in wild-type and I228M. Data are presented as mean ± SEM. Significant values are represented by *P < 0.05, **P < 0.01.