© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Cardiac sodium channel and inherited arrhythmia syndromes
aExperimental and Molecular Cardiology Group, Academic Medical Center, Amsterdam, The Netherlands
bDepartment of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands
cDepartment of Medical Physiology, Utrecht University Medical Center, Utrecht, The Netherlands
* Corresponding author. Tel.: +31-20-566-3265; fax: +31-20-697-5458 a.a.wilde@amc.uva.nl
Received 20 July 2000; accepted 30 October 2000
KEYWORDS Long QT syndrome; Sudden death; Ion channels; Na-channel; Sequence (DNA/RNA/prot)
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1 Introduction |
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The voltage-gated cardiac sodium channel is responsible for the generation of the rapid upstroke of the myocardial action potential and thereby plays a central role in excitability of myocardial cells. In addition, since the action potential upstroke velocity — in conjunction with the extent of intercellular communication via gap junctions [1] — also determines impulse conduction velocity in cardiac tissue, this channel also plays a vital role in impulse propagation. Mutations in the gene encoding this channel (SCN5A; Section 2.1) have been linked to three forms of primary electrical disease — the long QT syndrome (LQTS) [2], the Brugada syndrome (BS) [3] and cardiac conduction defects [4]. The elucidation of the pathophysiological mechanisms of these mutant Na+ channels would ultimately enable more specific pharmacological intervention in the management of these syndromes and other related arrhythmias.
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2 Cardiac sodium channel |
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The cardiac Na+ channel (see Ref. [5] for review)
2.1 
-Subunit
2.1.1 Permeation
2.1.2 Gating
2.2 β1-Subunit
2.3 Second messenger regulation
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3 Long QT syndrome |
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3.1 SCN5A mutations in LQTS3
3.2 Clinical features of LQTS3 and pharmacological intervention
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4 Brugada syndrome |
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4.1 Proposed mechanism for the ECG pattern and genesis of arrhythmias
4.2 SCN5A mutations in the Brugada syndrome
4.3 Patient management
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5 Isolated cardiac conduction defects |
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6 Synopsis |
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