Inhibition of Na+ channels ameliorates arrhythmias in a drug-induced model of Andersen-Tawil syndrome

These data suggest that cytosolic Na+ entry and its modulation of Ca2+ handling are necessary for arrhythmogenesis. During the loss of inward-rectifier K+ current function, not only Na+/Ca2+-exchange dominance but Na+ flux may determine arrhythmia burden. Therefore, selective inhibition of TTX-sensitive Na+ channels may offer a potential therapeutic target to alleviate arrhythmias during states of Ca2+ overload secondary to loss of inward-rectifier K+ current function without compromising the excitability reserve.