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Cardiac Na+ Channels as Therapeutic Targets for Antiarrhythmic Agents

  • Chapter
Basis and Treatment of Cardiac Arrhythmias

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 171))

Abstract

There are many factors that influence drug block of voltage-gated Na+ channels (VGSC). Pharmacological agents vary in conformation, charge, and affinity. Different drugs have variable affinities to VGSC isoforms, and drug efficacy is affected by implicit tissue properties such as resting potential, action potential morphology, and action potential frequency. The presence of polymorphisms and mutations in the drug target can also influence drug outcomes. While VGSCs have been therapeutic targets in the management of cardiac arrhythmias, their potential has been largely overshadowed by toxic side effects. Nonetheless, many VGSC blockers exhibit inherent voltage- and use-dependent properties of channel block that have recently proven useful for the diagnosis and treatment of genetic arrhythmias that arise from defects in Na+ channels and can underlie idiopathic clinical syndromes. These defective channels suggest themselves as prime targets of disease and perhaps even mutation specific pharmacological interventions.

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Authors and Affiliations

  1. Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630W. 168th St, New York, NY, 10032, USA

    I.W. Glaaser

  2. Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Medical College of Cornell University, 1300 York Avenue, LC-501E, New York, NY, 10021, USA

    C.E. Clancy

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Glaaser, I., Clancy, C. (2006). Cardiac Na+ Channels as Therapeutic Targets for Antiarrhythmic Agents. In: Basis and Treatment of Cardiac Arrhythmias. Handbook of Experimental Pharmacology, vol 171. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-29715-4_4

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