Cardiac late sodium current (Late INa)

The cardiac late sodium current (Late INa), also known as the cardiac persistent inward sodium current, is a sustained component of the sodium current that fails to fully inactivate during the plateau phase of the cardiac action potential (Antzelevitch et al., 2014). While the peak sodium current is responsible for rapid depolarization, the late current persists, contributing to the action potential duration and influencing intracellular ion balance. In pathological states such as myocardial ischemia, heart failure, and certain genetic mutations like Long QT Syndrome Type 3, this current is abnormally enhanced (Belardinelli et al., 2008). This enhancement leads to an overload of intracellular sodium, which subsequently drives calcium overload through the reverse mode of the sodium-calcium exchanger, causing electrical instability, delayed afterdepolarizations, and impaired diastolic relaxation (Shryock et al., 2013). Pharmacological targeting of the late sodium current aims to selectively inhibit this persistent component without significantly affecting the peak current necessary for normal cardiac conduction. Drugs like ranolazine and mexiletine are used to reduce the burden of arrhythmias and improve symptoms in conditions like chronic angina and LQT3 by restoring ionic homeostasis (PubMed: 16436574).

Other names

Cardiac persistent inward sodium currentPersistent sodium currentINa,LNon-inactivating sodium currentSCN5A-mediated late current

Selective inhibition of the late component of the inward sodium current (INa,L) to prevent intracellular sodium accumulation and subsequent calcium overload via the sodium-calcium exchanger (NCX).