The NaV1.5 channel, encoded by the SCN5A gene, is a voltage-gated sodium (NaV) channel found in skeletal muscle and heart1. It is TTX insensitive with an IC50 in the micromolar range. NaV1.5 is responsible for the upstroke of the cardiac action potential in both ventricular and atrial myocytes and is therefore critical for generation and propagation of the cardiac action potential in human heart. Block of this channel can lead to prolongation of the QRS interval of the electrocardiogram (ECG) and can have profound effects on the rate of cardiac depolarization and conduction velocity, thus causing potentially dangerous cardiac arrythmias. Furthermore, effects of NaV1.5 inactivation can modify cardiac repolarization. Given the importance of this channel in maintaining cardiac function, it has become an important target in compound safety screening.