Late sodium current in cardiomyocytes (Late INa)

The late sodium current in cardiomyocytes (late INa) is a small, persistent inward sodium current that flows during the plateau phase of the cardiac action potential, after the large transient (peak) sodium current has subsided[1][2][4]. Most cardiac sodium channels (mainly NaV1.5) inactivate rapidly within a few milliseconds after depolarization, but a subset fails to inactivate completely, allowing a sustained sodium influx. This current, although modest in amplitude (~0.5% of peak INa under normal conditions), has disproportionate effects on action potential duration, intracellular sodium and calcium loading, and contractility[1][5]. Enhanced late INa is observed in various pathological states, including inherited channelopathies (e.g., LQT3), heart failure, ischemia, and hypertrophy[1][2][4][5]. Abnormal augmentation of late sodium current contributes to arrhythmias by prolonging repolarization and promoting afterdepolarizations. Pharmacological inhibition of late sodium current (with drugs such as ranolazine, GS-967, and eleclazine) is being actively explored to treat arrhythmias, angina, and heart failure[2][3][4]. Selective targeting of this current represents a promising therapeutic strategy for several cardiovascular diseases, but careful attention is required to avoid impairing normal channel function or producing off-target adverse effects.

Other names

Late INaINaLPersistent sodium currentSustained sodium currentNon-inactivating sodium current

Inhibition of late sodium current: reduces action potential duration, lowers intracellular sodium and calcium overload, prevents arrhythmia triggers such as early/delayed afterdepolarizations (e.g., ranolazine, GS-967, eleclazine)[2][3][4]. Amplification of late sodium current (e.g., by ATX-II): used experimentally to study arrhythmogenic mechanisms, not a clinical therapy[1][3].