Pathophysiology and pharmacology of the cardiac late sodium current

The late sodium current (I-NaL) 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 I-NaL enhancement, which may contribute to the pathogenesis of both electrical and contractile dysfunction. For this reason, I-NaL has become an appealing pharmacological target, with a potentially broad range of therapeutic indications. The recent approval by the FDA of an I-NaL blocker (ranolazine) for clinical use justifies the increased interest in I-NaL as a pathogenic mechanism and the rapid evolution of the information concerning it. The review focuses on cardiac aspects of I-NaL enhancement; it deals with the origin of I-NaL, with its pathophysiological role and with the consequences of its pharmacological modulation. Both basic aspects and clinical evidence are discussed. (C) 2008 Elsevier Inc. All rights reserved.