Pathophysiology and pharmacology of the cardiac "late sodium current"

被引：145

作者：

Zaza, Antonio ^{[1
]}

Belardinelli, Luiz ^{[2
]}

Shryock, John C. ^{[2
]}

机构：

[1] Univ Milano Bicocca, Dipartimento Biotecnol & Biosci, I-20126 Milan, Italy

[2] CV Therapeut, Palo Alto, CA USA

来源：

PHARMACOLOGY & THERAPEUTICS | 2008年 / 119卷 / 03期

关键词：

late Na+ current; long QT syndromes; cardiac arrhythmias; myocardial remodeling; myocardial ischemia; Na+ channel blockers;

D O I：

10.1016/j.pharmthera.2008.06.001

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：326 / 339

页数：14

共 143 条

[1] Lidocaine and nisoldipine attenuate almakolant-induced dispersion of repolarization and early afterdepolarizations in vitro [J].