Objective: The human cardiac sodium channel plays a key role in controlling excitability in cardiac myocytes, and for impulse propagation through the specific conduction system in the heart. Mutations in the SCN5A gene, encoding the major cardiac sodium channel asubunit (hNa_v1.5), cause several inherited arrhythmogenic syndromes. Gain-of-function mutations underlie long QT syndrome subtype 3 (LQT3), and loss-of-function mutations cause Brugada syndrome (BrS) and cardiac conduction disease (CCD). We identified a novel SCN5A mutation, T1620K, leading to the rare combination of LQT3 and CCD in the same individuals. Lidocaine and ajmaline, commonly used antiarrhythmic drugs, normalized both QT intervals and conduction abnormalities. Methods: Mutant T1620K channels were characterized by the whole-cell patch-clamp technique in the absence and presence of lidocaine and ajmaline. Results: Electrophysiological measurements demonstrated that the T1620K mutation remarkably altered the properties of hNa_v1.5 channels. In particular, the voltage-dependence of the current decay time constants was largely lost. As a consequence, mutant channels inactivated faster than wild-type channels at potentials negative to -40 mV, resulting in less sodium inward current (loss-of-function), but significantly slower at potentials positive to -40 mV, resulting in an increased sodium inward current (gain-of-function). Both sodium channel blockers partially normalized the voltage-dependence of the channel inactivation. Conclusion: Our results suggest a mechanism for the simultaneous occurrence of LQT3 and CCD, and indicate the therapeutic potential of antiarrhythmic drugs by partially correcting defective ion channel kinetics.