Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart

被引:395
作者
Gaborit, Nathalie
Le Bouter, Sabrina
Szuts, Viktoria
Varro, Andras
Escande, Denis
Nattel, Stanley
Demolombe, Sophie
机构
[1] INSERM, Inst Thorax, U533, Fac Med, F-44035 Nantes, France
[2] Univ Nantes, Fac Med, F-4400 Nantes, France
[3] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada
[4] Univ Montreal, Montreal, PQ, Canada
[5] Univ Szeged, Dept Pharmacol & Pharmacotherapy, Szeged, Hungary
[6] Hungarian Acad Sci, Div Cardiovasc Pharmacol, Szeged, Hungary
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2007年 / 582卷 / 02期
关键词
D O I
10.1113/jphysiol.2006.126714
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The various cardiac regions have specific action potential properties appropriate to their electrical specialization, resulting from a specific pattern of ion-channel functional expression. The present study addressed regionally defined differential ion-channel expression in the non-diseased human heart with a genomic approach. High-throughput real-time RT-PCR was used to quantify the expression patterns of 79 ion-channel subunit transcripts and related genes in atria, ventricular epicardium and endocardium, and Purkinje fibres isolated from 15 non-diseased human donor hearts. Two-way non-directed hierarchical clustering separated atria, Purkinje fibre and ventricular compartments, but did not show specific patterns for epicardium versus endocardium, nor left- versus right-sided chambers. Genes that characterized the atria (versus ventricles) included Cx40, Kv1.5 and Kir3.1 as expected, but also Cav1.3, Cav3.1, Cav alpha 2 delta 2, Nav beta 1, TWIK1, TASK1 and HCN4. Only Kir2.1, RyR2, phospholamban and Kv1.4 showed higher expression in the ventricles. The Purkinje fibre expression-portrait (versus ventricle) included stronger expression of Cx40, Kv4.3, Kir3.1, TWIK1, HCN4, ClC6 and CALM1, along with weaker expression of mRNA encoding Cx43, Kir2.1, KChIP2, the pumps/exchangers Na+,K+-ATPase, NCX1, SERCA2, and the Ca2+-handling proteins RYR2 and CASQ2. Transcripts that were more strongly expressed in epicardium (versus endocardium) included Cav1.2, KChIP2, SERCA2, CALM3 and calcineurin-alpha. Nav1.5 and Nav beta 1 were more strongly expressed in the endocardium. For selected genes, RT-PCR data were confirmed at the protein level. This is the first report of the global portrait of regional ion-channel subunit-gene expression in the non-diseased human heart. Our data point to significant regionally determined ion-channel expression differences, with potentially important implications for understanding regional electrophysiology, arrhythmia mechanisms, and responses to ion-channel blocking drugs. Concordance with previous functional studies suggests that regional regulation of cardiac ion-current expression may be primarily transcriptional.
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收藏
页码:675 / 693
页数:19
相关论文
共 59 条
[21]   Comparison of ion-channel subunit expression in canine cardiac Purkinje fibers and ventricular muscle [J].
Han, W ;
Bao, WS ;
Wang, ZG ;
Nattel, S .
CIRCULATION RESEARCH, 2002, 91 (09) :790-797
[22]   Diversity of ion channel expression in health and disease [J].
Kääb, S ;
Näbauer, M .
EUROPEAN HEART JOURNAL SUPPLEMENTS, 2001, 3 (0K) :K31-K40
[23]   STRUCTURE AND FUNCTIONAL EXPRESSION OF A NEW MEMBER OF THE TETRODOTOXIN-SENSITIVE VOLTAGE-ACTIVATED SODIUM-CHANNEL FAMILY FROM HUMAN NEUROENDOCRINE CELLS [J].
KLUGBAUER, N ;
LACINOVA, L ;
FLOCKERZI, V ;
HOFMANN, F .
EMBO JOURNAL, 1995, 14 (06) :1084-1090
[24]   KChAP as a chaperone for specific K+ channels [J].
Kuryshev, YA ;
Gudz, TI ;
Brown, AM ;
Wible, BA .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2000, 278 (05) :C931-C941
[25]   In vivo cardiac gene transfer of Kv4.3 abrogates the hypertrophic response in rats after aortic stenosis [J].
Lebeche, D ;
Kaprielian, R ;
del Monte, F ;
Tomaselli, G ;
Gwathmey, JK ;
Schwartz, A ;
Hajjar, RJ .
CIRCULATION, 2004, 110 (22) :3435-3443
[26]   Potential ionic mechanism for repolarization differences between canine right and left atrium [J].
Li, DS ;
Zhang, LM ;
Kneller, J ;
Nattel, S .
CIRCULATION RESEARCH, 2001, 88 (11) :1168-1175
[27]   Endothelin-1-induced arrhythmogenic Ca2+ signaling is abolished in atrial myocytes of inositol-1,4,5-trisphosphate(IP3)-receptor type 2-deficient mice [J].
Li, XD ;
Zima, AV ;
Sheikh, F ;
Blatter, LA ;
Chen, J .
CIRCULATION RESEARCH, 2005, 96 (12) :1274-1281
[28]   Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method [J].
Livak, KJ ;
Schmittgen, TD .
METHODS, 2001, 25 (04) :402-408
[29]  
MAKITA N, 1994, J BIOL CHEM, V269, P7571
[30]   Muscarinic effects on action potential duration and its rate dependence in canine Purkinje fibers [J].
Malfatto, G ;
Zaza, A ;
Vanoli, E ;
Schwartz, PJ .
PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY, 1996, 19 (11) :2023-2026