Basic Cardiac Electrophysiology The Cardiac Sodium Channel: Gating Function and Molecular Pharmacology

rapid structural changes in response to the changing electrical field in the myocardium. Inherited mutations in SCN5A, the gene encoding the cardiac Na channel, provoke life-threatening cardiac arrhythmias, often by modifying these voltage-dependent conformational changes. These disorders (i.e., the long QT syndrome and Brugada syndrome) may serve as valuable models for understanding the mechanistic linkages between Na channel dysfunction and cardiac arrhythmias in more common, acquired conditions such as cardiac ischemia. In addition, the balance between therapeutic and adverse effects from Na channel blockade by antiarrhythmic compounds may be shifted by subtle alterations in Na channel function. This review examines recent studies that tie key loci in the Na channel primary sequence to its dynamic function, while examining the emerging themes linking Na channel structure, function, and pharmacology to inherited and acquired disorders of cardiac excitability. 2001 Academic Press K W: Sodium channel, Antiarrhythmic drugs, Lidocaine, Flecainide, Long QT syndrome, Brugada syndrome. the same time, Na channels are dynamic moleculesIntroduction that drastically change their structural con-formation on a sub-millisecond time scale in re-Voltage-gated sodium (Na) channels are trans