Pathophysiology and pharmacology of the cardiac “late sodium current”

The “late sodium current” (INaL) is a sustained component of the fast Na+ current of cardiac myocytes and neurons. As recently appreciated, common neurological and cardiac conditions are associated with abnormal INaL enhancement, which may contribute to the pathogenesis of both electrical and contractile dysfunction. For this reason, INaL has become an appealing pharmacological target, with a potentially broad range of therapeutic indications. The recent approval by the FDA of an INaL blocker (ranolazine) for clinical use justifies the increased interest in INaL as a pathogenic mechanism and the rapid evolution of the information concerning it. The review focuses on cardiac aspects of INaL enhancement; it deals with the origin of INaL, with its pathophysiological role and with the consequences of its pharmacological modulation. Both basic aspects and clinical evidence are discussed.