Human Heart Failure Is Associated With Abnormal C-Terminal Splicing Variants in the Cardiac Sodium Channel

Heart failure (HF) is associated with reduced cardiac Na channel (SCN5A) current. We hypothesized that abnormal transcriptional regulation of this ion channel during HF could help explain the reduced current. Using human hearts explanted at the transplantation, we have identified 3 human C-terminal...

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Bibliographic Details
Published in:Circulation research 2007-11, Vol.101 (11), p.1146-1154
Main Authors: Shang, Lijuan L, Pfahnl, Arnold E, Sanyal, Shamarendra, Jiao, Zhe, Allen, Jon, Banach, Kathrin, Fahrenbach, John, Weiss, Daiana, Taylor, W Robert, Zafari, A Maziar, Dudley, Samuel C
Format: Article
Language:English
Subjects:
Alternative Splicing
Animals
Biological and medical sciences
Cardiac dysrhythmias
Cardiology. Vascular system
Embryonic Stem Cells - metabolism
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Genetic Variation
Heart
Heart Failure - etiology
Heart Failure - genetics
Heart failure, cardiogenic pulmonary edema, cardiac enlargement
Humans
In Vitro Techniques
Medical sciences
Mice
NAV1.5 Voltage-Gated Sodium Channel
RNA, Messenger - genetics
Sodium Channels - genetics
Survival Rate
Transfection
Vertebrates: cardiovascular system
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Summary:Heart failure (HF) is associated with reduced cardiac Na channel (SCN5A) current. We hypothesized that abnormal transcriptional regulation of this ion channel during HF could help explain the reduced current. Using human hearts explanted at the transplantation, we have identified 3 human C-terminal SCN5A mRNA splicing variants predicted to result in truncated, nonfunctional channels. As compared with normal hearts, the explanted ventricles showed an upregulation of 2 of the variants and a downregulation of the full-length mRNA transcript such that the E28A transcript represented only 48.5% (P
ISSN:0009-7330
1524-4571
DOI:10.1161/CIRCRESAHA.107.152918