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

Nathalie Gaborit, Sabrina Le Bouter, V. Szűts, A. Varró, Denis Escande, Stanley Nattel, Sophie Demolombe

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Abstract

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, Cavα2δ2, Navβ1, 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-α. Nav1.5 and Navβ1 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.

Original languageEnglish
Pages (from-to)675-693
Number of pages19
JournalJournal of Physiology
Volume582
Issue number2
DOIs
Publication statusPublished - Jul 2007

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Ion Channels
Endocardium
Purkinje Fibers
Pericardium
Genes
Connexin 43
Ryanodine Receptor Calcium Release Channel
Calcineurin
Electrophysiology
Action Potentials
Cluster Analysis
Cardiac Arrhythmias
Real-Time Polymerase Chain Reaction
Proteins
Ions
Gene Expression
Polymerase Chain Reaction
Messenger RNA
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Physiology

Cite this

Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart. / Gaborit, Nathalie; Le Bouter, Sabrina; Szűts, V.; Varró, A.; Escande, Denis; Nattel, Stanley; Demolombe, Sophie.

In: Journal of Physiology, Vol. 582, No. 2, 07.2007, p. 675-693.

Research output: Contribution to journalArticle

Gaborit, Nathalie ; Le Bouter, Sabrina ; Szűts, V. ; Varró, A. ; Escande, Denis ; Nattel, Stanley ; Demolombe, Sophie. / Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart. In: Journal of Physiology. 2007 ; Vol. 582, No. 2. pp. 675-693.
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