Inactivation properties of wild type and mutant Nav1.4 and Nav1.5 sodium channels
| . | Inactivation . | Recovery from inactivation . | |||||||
|---|---|---|---|---|---|---|---|---|---|
| V1/2 (mV) . | k . | n . | Weighted τ (ms) . | Fast (τ [ms]) . | % (Fast) . | Slow (τ [ms]) . | % (Slow) . | n . | |
| Splice variants | |||||||||
| mNav1.5 | −82.1 ± 0.82 | −6.9 ± 0.16 | 34 | 12.7 ± 1.06 | 5.8 ± 0.22 | 79 | 38.1 ± 3.49 | 21 | 22 |
| mNav1.5e | −82.0 ± 0.52 | −7.2 ± 0.14 | 49 | 12.4 ± 0.41 | 6.2 ± 0.19 | 78 | 34.6 ± 1.24 | 22 | 46 |
| mNav1.5 + β3 | −76.3 ± 0.66 | −5.7 ± 0.12 | 12 | 5.2 ± 0.46 | 4.0 ± 0.20 | 83 | 11.1 ± 4.02 | 17 | 12 |
| mNav1.5e + β3 | −74.5 ± 0.55 | −6.2 ± 0.19 | 17 | 4.9 ± 0.24 | 3.5 ± 0.17 | 70 | 8.0 ± 1.24 | 30 | 15 |
| Single swaps | |||||||||
| mNav1.5-T206V | −81.3 ± 0.61 | −6.9 ± 0.35 | 21 | 13.2 ± 0.86 | 6.4 ± 0.25 | 78 | 38.6 ± 3.11 | 22 | 22 |
| mNav1.5e-V206T | −81.5 ± 0.49 | −7.5 ± 0.18 | 24 | 12.7 ± 0.40 | 6.1 ± 0.18 | 77 | 36.3 ± 2.04 | 23 | 23 |
| mNav1.5-T207S | −87.3 ± 1.05 | −7.4 ± 0.22 | 14 | 14.4 ± 1.00 | 7.3 ± 0.53 | 74 | 36.0 ± 2.69 | 26 | 11 |
| mNav1.5e-S207T | −83.4 ± 0.48 | −7.0 ± 0.09 | 25 | 14.0 ± 0.50 | 7.0 ± 0.28 | 78 | 39.9 ± 1.98 | 22 | 24 |
| mNav1.5-T207A | −81.9 ± 0.43 | −7.0 ± 0.21 | 25 | 15.1 ± 0.65 | 7.3 ± 0.26 | 78 | 43.8 ± 2.70 | 22 | 23 |
| mNav1.5e-S207A | −80.2 ± 0.62 | −7.6 ± 0.20 | 18 | 12.1 ± 0.46 | 5.5 ± 0.19 | 76 | 33.9 ± 2.14 | 24 | 17 |
| mNav1.5-F209N | −82.4 ± 0.77 | −8.0 ± 0.29 | 18 | 11.2 ± 0.76 | 5.5 ± 0.18 | 78 | 32.0 ± 3.40 | 22 | 18 |
| mNav1.5e-N209F | −79.9 ± 0.40 | −6.7 ± 0.09 | 21 | 11.3 ± 0.35 | 5.7 ± 0.16 | 80 | 35.9 ± 1.86 | 20 | 21 |
| mNav1.5-V210I | −81.1 ± 1.96 | −7.6 ± 0.42 | 11 | 14.4 ± 1.00 | 6.7 ± 0.50 | 79 | 44.3 ± 3.92 | 21 | 11 |
| mNav1.5e-I210V | −82.0 ± 0.45 | −6.9 ± 0.13 | 23 | 12.3 ± 0.52 | 5.8 ± 0.19 | 77 | 35.1 ± 2.28 | 23 | 19 |
| mNav1.5-D211K | −82.8 ± 0.59 | −7.3 ± 0.12 | 24 | 13.3 ± 0.56 | 7.2 ± 0.67 | 80 | 37.2 ± 1.96 | 20 | 21 |
| mNav1.5e-K211D | −80.3 ± 0.54 | −6.9 ± 0.12 | 30 | 10.4 ± 0.44 | 5.3 ± 0.23 | 80 | 31.5 ± 1.31 | 20 | 29 |
| mNav1.5-D211A | −79.8 ± 0.54 | −7.2 ± 0.22 | 15 | 11.0 ± 0.38 | 5.3 ± 0.21 | 78 | 32.8 ± 1.90 | 22 | 15 |
| mNav1.5e-K211A | −80.0 ± 0.48 | −6.7 ± 0.08 | 39 | 10.2 ± 0.37 | 5.2 ± 0.20 | 79 | 29.7 ± 1.53 | 21 | 34 |
| mNav1.5-V215L | −84.6 ± 0.54 | −6.4 ± 0.08 | 24 | 14.3 ± 0.71 | 7.3 ± 0.44 | 78 | 40.3 ± 2.36 | 22 | 21 |
| mNav1.5e-L215V | −82.8 ± 0.76 | −7.2 ± 0.11 | 20 | 13.9 ± 0.62 | 7.1 ± 0.36 | 76 | 36.9 ± 2.06 | 24 | 19 |
| mNav1.5-S234P | −81.3 ± 0.55 | −6.8 ± 0.15 | 20 | 11.9 ± 0.50 | 6.1 ± 0.25 | 79 | 34.2 ± 1.41 | 21 | 19 |
| mNav1.5e-P234S | −82.5 ± 0.65 | −7.9 ± 0.31 | 18 | 12.1 ± 0.44 | 5.9 ± 0.22 | 80 | 36.7 ± 1.56 | 20 | 18 |
| Double swaps | |||||||||
| mNav1.5-T207S-D211K | −82.7 ± 0.91 | −7.4 ± 0.30 | 25 | 18.7 ± 1.08 | 9.5 ± 0.41 | 75 | 49.2 ± 4.27 | 25 | 24 |
| mNav1.5e-S207T-K211D | −80.9 ± 0.51 | −6.5 ± 0.09 | 23 | 11.0 ± 0.28 | 5.5 ± 0.12 | 78 | 30.2 ± 1.11 | 22 | 23 |
| SCN4A | |||||||||
| Mys-P2A-mNav1.4 + β3 | −55.8 ± 0.66 | −5.3 ± 0.20 | 13 | 1.23 ± 0.18 | 1.1 ± 0.10 | 92 | 2.1 ± 0.81 | 8 | 12 |
| Mys-P2A-mNav1.4-T207S-D211K + β3 | −55.3 ± 0.36 | −5.4 ± 0.15 | 21 | 1.04 ± 0.07 | 0.96 ± 0.06 | 57 | 1.3 ± 0.22 | 43 | 17 |
| . | Inactivation . | Recovery from inactivation . | |||||||
|---|---|---|---|---|---|---|---|---|---|
| V1/2 (mV) . | k . | n . | Weighted τ (ms) . | Fast (τ [ms]) . | % (Fast) . | Slow (τ [ms]) . | % (Slow) . | n . | |
| Splice variants | |||||||||
| mNav1.5 | −82.1 ± 0.82 | −6.9 ± 0.16 | 34 | 12.7 ± 1.06 | 5.8 ± 0.22 | 79 | 38.1 ± 3.49 | 21 | 22 |
| mNav1.5e | −82.0 ± 0.52 | −7.2 ± 0.14 | 49 | 12.4 ± 0.41 | 6.2 ± 0.19 | 78 | 34.6 ± 1.24 | 22 | 46 |
| mNav1.5 + β3 | −76.3 ± 0.66 | −5.7 ± 0.12 | 12 | 5.2 ± 0.46 | 4.0 ± 0.20 | 83 | 11.1 ± 4.02 | 17 | 12 |
| mNav1.5e + β3 | −74.5 ± 0.55 | −6.2 ± 0.19 | 17 | 4.9 ± 0.24 | 3.5 ± 0.17 | 70 | 8.0 ± 1.24 | 30 | 15 |
| Single swaps | |||||||||
| mNav1.5-T206V | −81.3 ± 0.61 | −6.9 ± 0.35 | 21 | 13.2 ± 0.86 | 6.4 ± 0.25 | 78 | 38.6 ± 3.11 | 22 | 22 |
| mNav1.5e-V206T | −81.5 ± 0.49 | −7.5 ± 0.18 | 24 | 12.7 ± 0.40 | 6.1 ± 0.18 | 77 | 36.3 ± 2.04 | 23 | 23 |
| mNav1.5-T207S | −87.3 ± 1.05 | −7.4 ± 0.22 | 14 | 14.4 ± 1.00 | 7.3 ± 0.53 | 74 | 36.0 ± 2.69 | 26 | 11 |
| mNav1.5e-S207T | −83.4 ± 0.48 | −7.0 ± 0.09 | 25 | 14.0 ± 0.50 | 7.0 ± 0.28 | 78 | 39.9 ± 1.98 | 22 | 24 |
| mNav1.5-T207A | −81.9 ± 0.43 | −7.0 ± 0.21 | 25 | 15.1 ± 0.65 | 7.3 ± 0.26 | 78 | 43.8 ± 2.70 | 22 | 23 |
| mNav1.5e-S207A | −80.2 ± 0.62 | −7.6 ± 0.20 | 18 | 12.1 ± 0.46 | 5.5 ± 0.19 | 76 | 33.9 ± 2.14 | 24 | 17 |
| mNav1.5-F209N | −82.4 ± 0.77 | −8.0 ± 0.29 | 18 | 11.2 ± 0.76 | 5.5 ± 0.18 | 78 | 32.0 ± 3.40 | 22 | 18 |
| mNav1.5e-N209F | −79.9 ± 0.40 | −6.7 ± 0.09 | 21 | 11.3 ± 0.35 | 5.7 ± 0.16 | 80 | 35.9 ± 1.86 | 20 | 21 |
| mNav1.5-V210I | −81.1 ± 1.96 | −7.6 ± 0.42 | 11 | 14.4 ± 1.00 | 6.7 ± 0.50 | 79 | 44.3 ± 3.92 | 21 | 11 |
| mNav1.5e-I210V | −82.0 ± 0.45 | −6.9 ± 0.13 | 23 | 12.3 ± 0.52 | 5.8 ± 0.19 | 77 | 35.1 ± 2.28 | 23 | 19 |
| mNav1.5-D211K | −82.8 ± 0.59 | −7.3 ± 0.12 | 24 | 13.3 ± 0.56 | 7.2 ± 0.67 | 80 | 37.2 ± 1.96 | 20 | 21 |
| mNav1.5e-K211D | −80.3 ± 0.54 | −6.9 ± 0.12 | 30 | 10.4 ± 0.44 | 5.3 ± 0.23 | 80 | 31.5 ± 1.31 | 20 | 29 |
| mNav1.5-D211A | −79.8 ± 0.54 | −7.2 ± 0.22 | 15 | 11.0 ± 0.38 | 5.3 ± 0.21 | 78 | 32.8 ± 1.90 | 22 | 15 |
| mNav1.5e-K211A | −80.0 ± 0.48 | −6.7 ± 0.08 | 39 | 10.2 ± 0.37 | 5.2 ± 0.20 | 79 | 29.7 ± 1.53 | 21 | 34 |
| mNav1.5-V215L | −84.6 ± 0.54 | −6.4 ± 0.08 | 24 | 14.3 ± 0.71 | 7.3 ± 0.44 | 78 | 40.3 ± 2.36 | 22 | 21 |
| mNav1.5e-L215V | −82.8 ± 0.76 | −7.2 ± 0.11 | 20 | 13.9 ± 0.62 | 7.1 ± 0.36 | 76 | 36.9 ± 2.06 | 24 | 19 |
| mNav1.5-S234P | −81.3 ± 0.55 | −6.8 ± 0.15 | 20 | 11.9 ± 0.50 | 6.1 ± 0.25 | 79 | 34.2 ± 1.41 | 21 | 19 |
| mNav1.5e-P234S | −82.5 ± 0.65 | −7.9 ± 0.31 | 18 | 12.1 ± 0.44 | 5.9 ± 0.22 | 80 | 36.7 ± 1.56 | 20 | 18 |
| Double swaps | |||||||||
| mNav1.5-T207S-D211K | −82.7 ± 0.91 | −7.4 ± 0.30 | 25 | 18.7 ± 1.08 | 9.5 ± 0.41 | 75 | 49.2 ± 4.27 | 25 | 24 |
| mNav1.5e-S207T-K211D | −80.9 ± 0.51 | −6.5 ± 0.09 | 23 | 11.0 ± 0.28 | 5.5 ± 0.12 | 78 | 30.2 ± 1.11 | 22 | 23 |
| SCN4A | |||||||||
| Mys-P2A-mNav1.4 + β3 | −55.8 ± 0.66 | −5.3 ± 0.20 | 13 | 1.23 ± 0.18 | 1.1 ± 0.10 | 92 | 2.1 ± 0.81 | 8 | 12 |
| Mys-P2A-mNav1.4-T207S-D211K + β3 | −55.3 ± 0.36 | −5.4 ± 0.15 | 21 | 1.04 ± 0.07 | 0.96 ± 0.06 | 57 | 1.3 ± 0.22 | 43 | 17 |