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Sodium Ion Channelopathies

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Abstract

The voltage-gated cardiac sodium channel (Nav) is a multiple protein complex consisting of a ­pore-forming α-subunit, ancillary β-subunits and several regulatory proteins. Mutations in various sodium channel-related genes disrupt sodium channel function (gain-of-function or loss-of-­function) and lead to diseases such as Brugada syndrome, long QT syndrome, progressive cardiac conduction disease, sick sinus syndrome or atrial fibrillation. Furthermore, sodium channelopathies may cause sudden infant death syndrome (SIDS). Sodium ion channelopathies were initially regarded as inherited diseases without structural abnormalities. However, emerging evidence indicates that SCN5A mutations may be associated with structural changes. For instance, SCN5A mutations are considered possibly causative in idiopathic dilated cardiomyopathy. Interestingly, various single SCN5A mutations may show different clinical phenotypes in single patients or families. These cases are called overlap syndromes. The pathophysiologic basis of these overlap syndromes has not been fully elucidated: in some cases, different functional effects of the mutation during different phases of the cardiac action potential may be involved, while, in others, various modifiers, including SCN5A and other gene mutations/polymorphism may be involved. On the other hand, some SCN5A mutations may be not causal but just a bystander of a sodium channelopathy. This chapter aims to summarize the current knowledge on the cardiac sodium channel, diseases caused by mutations in sodium channel encoding genes, and discuss the proposed underlying mechanisms.

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Abbreviations

AF:

Atrial fibrillation

ARVC:

Arrhythmogenic right ventricular cardiomyopathy

BrS:

Brugada syndrome

DCM:

Dilated cardiomyopathy

LQTS:

Long QT syndrome

LQT3:

Long QT syndrome type 3

PCCD:

Progressive cardiac conduction disease

SCD:

Sudden cardiac death

SIDS:

Sudden infant death syndrome

SSS:

Sick sinus syndrome

VF:

Ventricular fibrillation

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Authors and Affiliations

  1. Department of Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands

    Yuka Mizusawa MD & Arthur A. M. Wilde MD, PhD

  2. Department of Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, Room K2-109, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands

    Hanno L. Tan MD, PhD

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  1. Yuka Mizusawa MD
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  2. Arthur A. M. Wilde MD, PhD
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  3. Hanno L. Tan MD, PhD
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Correspondence to Hanno L. Tan MD, PhD .

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  1. , Department of Internal Medicine, UMDNJ-RWJ Medical School, Robert Wood Johnson Pl. 1, New Brunswick, 08903-0019, New Jersey, USA

    Ihor Gussak

  2. , Gordon K. Moe Scholar, Masonic Medical Research Laboratory, Bleecker Street, Utica, 13501-1787, New York, USA

    Charles Antzelevitch

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Mizusawa, Y., Wilde, A.A.M., Tan, H.L. (2013). Sodium Ion Channelopathies. In: Gussak, I., Antzelevitch, C. (eds) Electrical Diseases of the Heart. Springer, London. https://doi.org/10.1007/978-1-4471-4881-4_11

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