Sodium channel protein type 5 subunit alpha (NaV1.5) (NaV1.5)

The Sodium channel protein type 5 subunit alpha (NaV1.5) is the principal voltage-gated sodium channel in cardiac myocytes, forming the pore for rapid Na+ influx that drives the upstroke of the action potential and enables impulse conduction across the heart. Encoded by the SCN5A gene on chromosome 3, it features four homologous domains with voltage-sensing S4 segments and a selectivity filter pore, operating in closed, open, and inactivated states modulated by voltage and interacting beta-subunits like SCN1B-SCN4B. Expressed abundantly in working myocardium and conduction tissue with a transmural gradient, NaV1.5 sustains excitability but produces minor late/persistent currents implicated in pathology. Loss-of-function mutations cause Brugada syndrome, progressive conduction disease, sick sinus syndrome, and atrial fibrillation via reduced excitability, while gain-of-function variants lead to Long QT syndrome type 3 through prolonged depolarization and increased late Na+ current. As a longstanding pharmacological target, it is modulated by Class I antiarrhythmics that block peak or late currents to treat ventricular tachycardia or atrial fibrillation, though with risks of proarrhythmia in structurally compromised hearts.

Other names

SCN5ASodium voltage-gated channel alpha subunit 5Voltage-gated sodium channel subunit alpha Nav1.5Cardiac sodium channelSodium channel protein cardiac muscle subunit alphaHB2CMD1EVF1LQT3SSS1HH1

Sodium channel blockade (peak sodium current inhibition), Reduction of late sodium current (I_Na,L), Modulation of channel inactivation and voltage dependence