Late sodium current and calcium homeostasis in arrhythmogenesis

The cardiac late sodium current (I-Na,I-late) is the small sustained component of the sodium current active during the plateau phase of the action potential. Several studies demonstrated that augmentation of the current can lead to cardiac arrhythmias; therefore, I-Na,I-late is considered as a promising antiarrhythmic target. Fundamentally, enlarged I-Na,I-late increases Na+ influx into the cell, which, in turn, is converted to elevated intracellular Ca2+ concentration through the Na+/Ca2+ exchanger. The excessive Ca2+ load is known to be proarrhythmic. This review describes the behavior of the voltage-gated Na+ channels generating I-Na,I-late in health and disease and aims to discuss the physiology and pathophysiology of Na+ and Ca2+ homeostasis in context with the enhanced I-Na,I-late demonstrating also the currently accessible antiarrhythmic choices.

Automated summary

The cardiac late sodium current (I-Na, I-late) plays a role during the plateau phase of the action potential and augmentation of this current can lead to cardiac arrhythmias, making it a promising antiarrhythmic target. Increased I-Na, I-late results in greater Na+ influx into the cell, which in turn raises intracellular Ca2+ levels, potentially causing arrhythmias.