Sodium channel protein type 5 subunit alpha (Naᵥ1.5) (Naᵥ1.5)

The Sodium channel protein type 5 subunit alpha, commonly known as Naᵥ1.5, is a critical voltage-gated ion channel primarily expressed in the heart's myocardium and conduction system (Wikipedia, 2024). It is responsible for the rapid influx of sodium ions during the initial upstroke (Phase 0) of the cardiac action potential, which is essential for the initiation and propagation of electrical impulses throughout the heart (NIH, 2024). Mutations in the SCN5A gene, which encodes Naᵥ1.5, are linked to various inherited cardiac channelopathies, including Brugada syndrome and Long QT syndrome type 3 (MedlinePlus, 2024). Loss-of-function mutations typically lead to conduction slowing and Brugada syndrome, while gain-of-function mutations result in persistent sodium currents and Long QT syndrome (Frontiers in Pharmacology, 2019). Pharmacologically, Naᵥ1.5 is the primary target for Class I antiarrhythmic drugs like flecainide and lidocaine, which modulate cardiac excitability by blocking the channel's pore (NIH, 2024). Additionally, selective inhibition of the late sodium current by drugs like ranolazine is used to treat chronic angina and certain arrhythmias by reducing intracellular calcium overload (NIH, 2025). Beyond its cardiac role, Naᵥ1.5 has been implicated in cancer metastasis and immune responses, making it a subject of broader therapeutic interest (NIH, 2024). Safety concerns regarding Naᵥ1.5 modulation include the risk of proarrhythmia and conduction block, particularly in patients with underlying structural heart disease (NIH, 2024).

Other names

SCN5ACardiac voltage-gated sodium channel Naᵥ1.5Sodium voltage-gated channel alpha subunit 5HB1CDCD2CMD1ECMPD2HB2HBBDHH1ICCDIVFLQT3PFHB1SSS1VF1

Sodium channel blockade (Class I antiarrhythmics) and inhibition of late sodium current