Cardiac-specific overexpression of SCN5A gene leads to shorter P wave duration and PR interval in transgenic mice

被引：31

作者：

Zhang, Teng

Yong, Sandro L.

Tian, Xiao-Li

Wang, Qing K.

机构：

[1] Cleveland Clin, Lerner Res Inst NE40, Ctr Cardiovasc Genet, Dept Cardiovasc Med, Cleveland, OH 44195 USA

[2] Case Western Reserve Univ, Cleveland Clin Lerner Coll Med, Dept Mol Med, Cleveland, OH 44195 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2007年 / 355卷 / 02期

关键词：

cardiac sodium channel gene SCN5A; long QT syndrome (LQTS); ventricular arrhythmias or tachycardia (VT); transgenic mice; electrocardiogram (ECG); P wave and PR interval; sodium current;

D O I：

10.1016/j.bbrc.2007.01.170

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：

The Cardiac sodium channel gene SCN5A plays a critical role in cardiac electrophysiology and its mutations, either gain- or loss-of-functions, are associated with lethal arrhythmias. In this study, we investigated the effect of overexpression of SCN5A on the cardiac phenotype in a transgenic mouse model (TG-WT L10). Compared to NTG mice, heart rate, QRS duration, and QT intervals remained unchanged in TG-WT mice. Moreover, no spontaneous ventricular arrhythmias were detected in TG-WT hearts. Despite these results, a mild, irregular cardiac phenotype was observed in TG-WT mice. The P wave and PR interval were significantly shorter in TG-WT compared with NTG mice (P, 8.8 +/- 0.8 ms vs. 12.6 +/- 0.9 ms; PR, 12.5 +/- 2 ms vs. 33.5 +/- 0.7 ms). Furthermore, spontaneous premature atrial contractions were often detected in TG-WT mice. These results suggest that the expression level of the SCN5A gene is a determinant for the length of the P wave duration and PR interval on electrocardiograms (ECG). (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：444 / 450

页数：7

共 21 条

[1] Genetic basis and molecular mechanism for idiopathic: ventricular fibrillation [J].

Chen, QY ;

Kirsch, GE ;

Zhang, DM ;

Brugada, R ;

Brugada, J ;

Brugada, P ;

Potenza, D ;

Moya, A ;

Borggrefe, M ;

Breithardt, G ;

Ortiz-Lopez, R ;

Wang, Z ;

Antzelevitch, C ;

O'Brien, RE ;

Schulze-Bahr, E ;

Keating, MT ;

Towbin, JA ;

Wang, Q .

NATURE, 1998, 392 (6673) :293-296

[2] PRIMARY STRUCTURE AND FUNCTIONAL EXPRESSION OF THE HUMAN CARDIAC TETRODOTOXIN-INSENSITIVE VOLTAGE-DEPENDENT SODIUM-CHANNEL [J].

GELLENS, ME ;

GEORGE, AL ;

CHEN, LQ ;

CHAHINE, M ;

HORN, R ;

BARCHI, RL ;

KALLEN, RG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (02) :554-558

[3] Abrupt rate accelerations or premature beats cause life-threatening arrhythmias in mice with long-QT3 syndrome [J].

Nuyens, D ;

Stengl, M ;

Dugarmaa, S ;

Rossenbacker, T ;

Compernolle, V ;

Rudy, Y ;

Smits, JF ;

Flameng, W ;

Clancy, CE ;

Moons, L ;

Vos, MA ;

Dewerchin, M ;

Benndorf, K ;

Collen, D ;

Carmeliet, E ;

Carmeliet, P .

NATURE MEDICINE, 2001, 7 (09) :1021-1027

[4] Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a [J].

Papadatos, GA ;

Wallerstein, PMR ;

Head, CEG ;

Ratcliff, R ;

Brady, PA ;

Benndorf, K ;

Saumarez, RC ;

Trezise, AEO ;

Huang, CLH ;

Vandenberg, JI ;

Colledge, WH ;

Grace, AA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (09) :6210-6215

[5] Overlap syndrome of cardiac sodium channel disease in mice carrying the equivalent mutation of human SCN5A-1795insD [J].

Remme, Carol Ann ;

Verkerk, Arie O. ;

Nuyens, Dieter ;

van Ginneken, Antoni C. G. ;

van Brunschot, Sandra ;

Belterman, Charly N. W. ;

Wilders, Ronald ;

van Roon, Marian A. ;

Tan, Hanno L. ;

Wilde, Arthur A. M. ;

Carmeliet, Peter ;

de Bakker, Jacques M. T. ;

Veldkamp, Marieke W. ;

Bezzina, Connie R. .

CIRCULATION, 2006, 114 (24) :2584-2594

[6] Mouse model of SCN5A-linked hereditary Lenegre's disease -: Age-related conduction slowing and myocardial fibrosis [J].

Royer, A ;

van Veen, TAB ;

Le Bouter, S ;

Marionneau, C ;

Griol-Charhbili, V ;

Léoni, AL ;

Steenman, M ;

van Rijen, HVM ;

Demolombe, S ;

Goddard, CA ;

Richer, C ;

Escoubet, B ;

Jarry-Guichard, T ;

Colledge, WH ;

Gros, D ;

de Bakker, JMT ;

Grace, AA ;

Escande, D ;

Charpentier, F .

CIRCULATION, 2005, 111 (14) :1738-1746

[7] Transgenic mouse model of ventricular preexcitation and atrioventricular reentrant tachycardia induced by an AMP-activated protein kinase loss-of-function mutation responsible for Wolff-Parkinson-White syndrome [J].

Sidhu, JS ;

Rajawat, YS ;

Rami, TG ;

Gollob, MH ;

Wang, ZN ;

Yuan, RY ;

Marian, AJ ;

DeMayo, FJ ;

Weilbacher, D ;

Taffet, GE ;

Davies, JK ;

Carling, D ;

Khoury, DS ;

Roberts, R .

CIRCULATION, 2005, 111 (01) :21-29

[8] A sodium-channel mutation causes isolated cardiac conduction disease [J].

Tan, HL ;

Bink-Boelkens, MTE ;

Bezzina, CR ;

Viswanathan, PC ;

Beaufort-Krol, GCM ;

van Tintelen, PJ ;

van den Berg, MP ;

Wilde, AAM ;

Balser, JR .

NATURE, 2001, 409 (6823) :1043-1047

[9]

Tian Xiao-Li, 2006, V129, P69

[10] Optical mapping of ventricular arrhythmias in LQTS mice with SCN5A mutation N1325S [J].

Tian, Xiao-Li ;

Cheng, Yuanna ;

Zhang, Teng ;

Liao, Mei-Ling Chang ;

Yong, Sandro L. ;

Wang, Qing K. .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 352 (04) :879-883

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