Table 1.
Clinically relevant “causes” of late INa and possible mechanisms. Remodeling means alteration of the Na channel complex in a way that favors late INa by for example the disappearance of subunits [49]. References for these clinically relevant, and many other experimentally relevant causes of late INa have been recently reviewed [7]
| Genetic | |
| LQT3 | Direct Biophysical |
| LQT9 | Enhanced Nitrosylation |
| LQT10 | ? |
| LQT12 | Enhanced Nitrosylation |
| Acquired | |
| Hypertrophy | Stretch, altered signaling, remodeling |
| Heart Failure | Stretch, altered signaling, remodeling |
| Ischemia | Acidosis, metabolites (LPC) |
| Diabetes | Cardiomyopathy, altered signaling |
| Molecules | |
| Carbon Monoxide | ? |
| Acidosis | ? |
| LPC (ischemic metabolite) | PKC? |
| ROS (H2O2) | CamK? |
| Drugs | |
| Dofetilide | PI3K inhibition |
| Sotalol | PI3K inhibition |
| Erythromycin | PI3K inhibition |
| Thioridazine | PI3K inhibition |
| Nilotinib | PI3K inhibition |
| Cell signaling | |
| nNOS Nitrosylation | direct on NaV1.5 |
| CamK Phosphorylation | direct on NaV1.5 |
| PI3K-Akt pathway inhibition | ? |
| PKC Phosphorylation | direct on NaV1.5 |