Table 6.
Variations of biophysical parameters compared to wild type channels for five equivalent mutations identified in Nav1.4 and Nav1.5 that have been studied extensively in patch clamp.
| Subunit | Mutation | Pathologies | Cell model | ΔV0.5 act (mV) | ΔV0.5 fast inac (mV) | Mutant/WT Fast inact tau * | Mutant/WT i persistent | References |
|---|---|---|---|---|---|---|---|---|
| Nav1.4 | I141V | SCM | HEK | −10 | 0 | 77% at −10 mV | ? | Petitprez et al., 2008; Amarouch et al., 2014 |
| Nav1.5 | I141V | ExPVC | HEK | −8 | 0 | 86% | ? | Amarouch et al., 2014; Swan et al., 2014 |
| Nav1.4 | Q270K |  |
HEK | 1.3 | 12.5 | 168% at −25 mV | 200% | Carle et al., 2009 |
| Nav1.5 | Q270K | CHO | 5.8 | 9.9 | 260% at −25 mV | 338% | Calloe et al., 2011 | |
| Nav1.4 | N440K | Normo Hyper PP | HEK | 0 | 7.1 | 100% | 800% | Lossin et al., 2012 |
| Nav1.5 | N406K | LQT3 | CHO | 8.6 | 0 | 217% | 550% | Kato et al., 2014 |
| Nav1.4 | V445M | Myotonia | HEK | −4.1 | −4.9 | ? | 1400% | Takahashi and Cannon, 1999 |
| Nav1.5 | V411M | LQT3 | HEK | −8.1 | −7.9 | 75% | 176% | Horne et al., 2011 |
| Nav1.4 | V1589M | overlap PC-SCM | HEK | 0 | 5.4 | 100% | 362% | Mitrovic et al., 1994 |
| Nav1.5 | V1763M | LQT3 | hiPSC-CMs | 0 | 16.8 | ? | 486% | Ma et al., 2013 |
Recording were all done at room temperature (except for Nav1.4 N440K: not indicated).
*
Fast inactivation tau is measured at −30 mV except when indicated.
Green, consistent effect; red, inconsistent effect; SCM, Sodium Channel Myotonia; ExPVC, exercise-induced polymorphic ventricular premature complexes; PC, Paramyotonia Congenita; LQT3, Type 3 Long QT syndrome; Normo, Hyper PP, Normo, Hyper-kalemic Periodic Paralysis; Conduc, conduction disease; hiPSC-CMs, cardiomyocytes generated from human induced pluripotent cells; ?, means not determined.