Phenotype, genotype, and cellular physiology: Need for clarity in characterization

Abstract

The voltage-dependent sodium channel α-subunit is encoded by the SCN5A gene and carries INa, which is the current predominantly responsible for the rapid upstroke of the action potential in the heart. 1,2 INa is central to the control of excitability and conduction in atrial and ventricular myocardial tissue and the specialized conduction system Purkinje fibers. Mutations in SCN5A have been associated with several inherited cardiac conditions, including long QT syndrome type 3 (LQT3), Brugada syndrome (BrS), familial atrial fibrillation, sudden infant death syndrome, mixed conduction disease, and dilated cardiomyopathy.