Na_v1.5

Na_v1.5, encoded by SCN5A, is the main cardiac voltage-gated sodium channel and predominates the inward sodium current, I_Na, that drives the fast upstroke of the cardiac action potential^[1]. Mechanistically, Na_v1.5 supports myocardial excitability and electrical conduction, while its expression, localization, and biophysical properties are regulated through transcript structure, post-translational modification, and interacting proteins^[2]. In disease models, SCN5A mutations and altered Na_v1.5 function are linked to long QT syndrome, Brugada syndrome, conduction disease, cardiomyopathy, atrial fibrillation, and heart failure-associated arrhythmogenesis^[1][2][3]. Compared with related sodium-channel isoforms, Na_v1.5 is defined by its cardiac predominance, while the neonatal splice variant nNa_v1.5 shows distinct relevance in cancer-cell models^[4]. In MDA-MB-231 breast cancer cells, nNa_v1.5 potentiates invasive behavior, and Na_v1.5 regulates epithelial-to-mesenchymal transition and invasiveness through salt-inducible kinase-1^[4][5]. For experimental applications, nNa_v1.5 blockers, propranolol, ranolazine combinations, and eslicarbazepine-related compounds have been used to inhibit Na_v1.5 current or cancer-cell invasion in vitro^[6][7][8].