SCN5A channelopathies - An update on mutations and mechanisms

被引：123

作者：

Zimmer, Thomas ^{[1
]}

Surber, Ralf ^{[2
]}

机构：

[1] Univ Jena, Inst Physiol 2, D-07743 Jena, Germany

[2] Univ Jena, Dept Internal Med, D-07740 Jena, Germany

来源：

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY | 2008年 / 98卷 / 2-3期

关键词：

Brugada syndrome; Cardiac conduction disease; LQT3; SCN5A;

D O I：

10.1016/j.pbiomolbio.2008.10.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Voltage-gated Na- channels mediate the rapid upstroke of the action potential in excitable tissues. Na(v)1.5, encoded by the SCN5A gene, is the predominant isoform in the heart. Mutations in SCN5A are associated with distinct cardiac excitation disorders often resulting in life-threatening arrhythmias. This review outlines the Currently known SCN5A mutations linked to three distinct cardiac rhythm disorders: long QT syndrome Subtype 3 (LQT3), Brugada syndrome (BS), and cardiac conduction disease (CCD). Electrophysiological properties of the mutant channels are summarized and discussed in terms of Na+ Channel structure-function relationships and regarding molecular mechanisms Underlying the respective cardiac dysfunction. Possible reasons for less convincing genotype-phenotype correlations are suggested. (C) 2008 Elsevier Ltd. All rights reserved

引用

收藏

页码：120 / 136

页数：17

相关论文

共 197 条

[1] Regulation of the voltage-gated cardiac sodium channel Nav1.5 by interacting proteins [J].

Abriel, H ;

Kass, RS .

TRENDS IN CARDIOVASCULAR MEDICINE, 2005, 15 (01) :35-40

[2] Novel arrhythmogenic mechanism revealed by a Long-QT syndrome mutation in the cardiac Na+ channel [J].

Abriel, H ;

Cabo, C ;

Wehrens, XHT ;

Rivolta, I ;

Motoike, HK ;

Memmi, M ;

Napolitano, C ;

Priori, SG ;

Kass, RS .

CIRCULATION RESEARCH, 2001, 88 (07) :740-745

[3] Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: Implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing [J].

Ackerman, MJ ;

Splawski, I ;

Makielski, JC ;

Tester, DJ ;

Will, ML ;

Timothy, KW ;

Keating, MT ;

Jones, G ;

Chadha, M ;

Burrow, CR ;

Stephens, JC ;

Xu, CB ;

Judson, R ;

Curran, ME .

HEART RHYTHM, 2004, 1 (05) :600-607

[4] Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome [J].

Ackerman, MJ ;

Siu, BL ;

Sturner, WQ ;

Tester, DJ ;

Valdivia, CR ;

Makielski, JC ;

Towbin, JA .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 286 (18) :2264-2269

[5] A novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome [J].

Akai, J ;

Makita, N ;

Sakurada, H ;

Shirai, N ;

Ueda, K ;

Kitabatake, A ;

Nakazawa, K ;

Kimura, A ;

Hiraoka, M .

FEBS LETTERS, 2000, 479 (1-2) :29-34

[6] Cardiac sodium channel gene variants and sudden cardiac death in women [J].

Albert, Christine M. ;

Nam, Edwin G. ;

Rimm, Eric B. ;

Jin, Hong Wei ;

Hajjar, Roger J. ;

Hunter, David J. ;

MacRae, Calum A. ;

Ellinor, Patrick T. .

CIRCULATION, 2008, 117 (01) :16-23

[7] Brugada syndrome - Clinical data and suggested pathophysiological mechanism [J].

Alings, M ;

Wilde, A .

CIRCULATION, 1999, 99 (05) :666-673

[8] Novel Brugada syndrome-causing mutation in ion-conducting pore of cardiac Na+ channel does not affect ion selectivity properties [J].

Amin, AS ;

Verkerk, AO ;

Bhuiyan, ZA ;

Wilde, AAM ;

Tan, HL .

ACTA PHYSIOLOGICA SCANDINAVICA, 2005, 185 (04) :291-301

[9] Genetic basis of Brugada syndrome [J].

Antzelevitch, Charles .

HEART RHYTHM, 2007, 4 (06) :756-757

[10] Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-Segment elevation, short QT intervals, and sudden cardiac death [J].

Antzelevitch, Charles ;

Pollevick, Guido D. ;

Cordeiro, Jonathan M. ;

Casis, Oscar ;

Sanguinetti, Michael C. ;

Aizawa, Yoshiyasu ;

Guerchicoff, Alejandra ;

Pfeiffer, Ryan ;

Oliva, Antonio ;

Wollnik, Bernd ;

Gelber, Philip ;

Bonaros, Elias P., Jr. ;

Burashnikov, Elena ;

Wu, Yuesheng ;

Sargent, John D. ;

Schickel, Stefan ;

Oberheiden, Ralf ;

Bhatia, Atul ;

Hsu, Li-Fern ;

Haissaguerre, Michel ;

Schimpf, Rainer ;

Borggrefe, Martin ;

Wolpert, Christian .

CIRCULATION, 2007, 115 (04) :442-449

← 1 2 3 4 5 6 7 8 9 10 →