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Late Sodium Current Inhibition in Acquired and Inherited Ventricular (dys)function and Arrhythmias

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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 (INaL) represents a functionally relevant contributor to cardiomyocyte (electro)physiology. Many aspects of INaL 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 INaL 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.

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Acknowledgments

Dr. C.A. Remme is supported by the InterUniversity Cardiology Institute of the Netherlands (ICIN; 061.02) and the Division for Earth and Life Sciences (ALW) with financial aid from the Netherlands Organization for Scientific Research (NWO; 836.09.003).

Disclosure

Dr. C.A. Remme receives a research grant from Gilead Sciences.

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  1. Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Carol Ann Remme & Arthur A. M. Wilde

  2. Department of Experimental Cardiology, Academic Medical Center, Room K2-110, PO Box 22700, 1100 DE, Amsterdam, The Netherlands

    Carol Ann Remme

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Remme, C.A., Wilde, A.A.M. Late Sodium Current Inhibition in Acquired and Inherited Ventricular (dys)function and Arrhythmias. Cardiovasc Drugs Ther 27, 91–101 (2013). https://doi.org/10.1007/s10557-012-6433-x

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