Late sodium current and calcium homeostasis in arrhythmogenesis.

The cardiac late sodium current (I _Na,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,late is considered as a promising antiarrhythmic target. Fundamentally, enlarged I _Na,late increases Na ⁺ influx into the cell, which, in turn, is converted to elevated intracellular Ca ²⁺ concentration through the Na ⁺ /Ca ²⁺ exchanger. The excessive Ca ²⁺ load is known to be proarrhythmic. This review describes the behavior of the voltage-gated Na ⁺ channels generating I _Na,late in health and disease and aims to discuss the physiology and pathophysiology of Na ⁺ and Ca ²⁺ homeostasis in context with the enhanced I _Na,late demonstrating also the currently accessible antiarrhythmic choices.