The aim of this study was to generate and characterize a transgenic zebrafish arrhythmia model harboring the pathogenic human cardiac sodium channel mutation SCN5A-D1275N, that has been robustly associated with a range of cardiac phenotypes, including conduction disease, sinus node dysfunction, atrial and ventricular arrhythmias, and dilated cardiomyopathy in humans and in mice.
Our experimental and computational analysis of the E161K mutation suggests that a loss of sodium channel function is not only associated with Brugada syndrome and conduction disease, but may also cause sinus node dysfunction in carriers of this mutation.