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. © 2008 Elsevier Inc. All rights reserved.