title: Late sodium current inhibition in acquired and inherited ventricular (dys)function and arrhythmias.
abstract: The late sodium current has been increasingly recognized for its mechanistic role in various cardiovascular pathologies, including angina pectoris, myocardial ischemia, atrial fibrillation, heart failure and congenital long QT syndrome. Although relatively small in magnitude, the late sodium current (I(NaL)) represents a functionally relevant contributor to cardiomyocyte (electro)physiology. Many aspects of I(NaL) itself are as yet still unresolved, including its distribution and function in different cell types throughout the heart, and its regulation by sodium channel accessory proteins and intracellular signalling pathways. Its complexity is further increased by a close interrelationship with the peak sodium current and other ion currents, hindering the development of inhibitors with selective and specific properties. Thus, increased knowledge of the intricacies of the complex nature of I(NaL) during distinct cardiovascular conditions and its potential as a pharmacological target is essential. Here, we provide an overview of the functional and electrophysiological effects of late sodium current inhibition on the level of the ventricular myocyte, and its potential cardioprotective and anti-arrhythmic efficacy in the setting of acquired and inherited ventricular dysfunction and arrhythmias.
authors.affiliation: Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. c.a.remme@amc.uva.nl
authors.forename: Carol Ann
authors.initials: CA
authors.lastname: Remme
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D030342:Genetic Diseases, Inborn / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016896:Treatment Outcome; D018754:Ventricular Dysfunction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D061567:Voltage-Gated Sodium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D000889:Anti-Arrhythmia Agents; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels