Mechanistic Insights into Sodium Currents and Cardiac Arrhythmias: Innovations in Therapeutic Strategies

Cardiac sodium currents from Nav1.5 channels play a central role in determining the excitability, conduction velocity, and electrical stability of the heart. The fast inward sodium current (INa) underlies the atrial, Purkinje fibers and ventricular action potential upstroke and rapid impulse propagation, while the late sodium current (late INa) contributes to action potential duration and, when excessive, promotes arrhythmogenic activity. More recently, the Nav1.8 channel encoded by SCN10A has emerged as a key player in modulating cardiac excitability and arrhythmic risk. Altered sodium currents function has been linked to a wide spectrum of cardiac rhythm disorders, including atrial fibrillation and ventricular tachyarrhythmias. Despite major advances in deciphering the molecular mechanisms underlying sodium channel function, important gaps remain regarding the integration of these currents within the complex environment of pathological cardiac remodeling and their potential as therapeutic targets.

This Research Topic aims to elucidate the mechanistic interplay between distinct sodium currents and the development of cardiac arrhythmias, while fostering advances in targeted therapeutic strategies. This Research Topic seeks to gather contributions that define how abnormalities in Nav1.5, late INa, and Nav1.8 currents influence action potential dynamics, calcium homeostasis, and conduction patterns under physiological and diseased conditions. By combining molecular and electrophysiological insights with translational and clinical studies, this Research Topic encourages research that bridges mechanistic discoveries to therapeutic innovations. Investigations exploring emerging sodium current modulators - such as late INa inhibitors (e.g., Ranolazine, GS 967) and Nav1.8 specific blockers (e.g., A 803467), will be central to advancing precision therapies for arrhythmia prevention and management.

The scope of this Research Topic encompasses molecular, cellular, computational, and translational aspects of sodium channels and arrhythmia research. To gather further insights into sodium current regulation and therapeutic potential, we welcome submissions addressing, but not limited to, the following themes:
o Biophysical mechanisms of Nav1.5, late INa, and Nav1.8 currents
o Genetic and post-translational modulation of sodium channels
o Pathophysiological mechanisms linking sodium currents to arrhythmias
o Therapeutic approaches targeting pathological sodium currents
o Computational and clinical investigations of sodium channel dysfunction