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.