Mutant Caveolin-3 Induces Persistent Late Sodium Current and Is Associated With Long-QT Syndrome
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- 14 November 2006
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 114 (20), 2104-2112
- https://doi.org/10.1161/circulationaha.106.635268
Abstract
Background— Congenital long-QT syndrome (LQTS) is a primary arrhythmogenic syndrome stemming from perturbed cardiac repolarization. LQTS, which affects ≈1 in 3000 persons, is 1 of the most common causes of autopsy-negative sudden death in the young. Since the sentinel discovery of cardiac channel gene mutations in LQTS in 1995, hundreds of mutations in 8 LQTS susceptibility genes have been identified. All 8 LQTS genotypes represent primary cardiac channel defects (ie, ion channelopathy) except LQT4, which is a functional channelopathy because of mutations in ankyrin-B. Approximately 25% of LQTS remains unexplained pathogenetically. We have pursued a “final common pathway” hypothesis to elicit novel LQTS-susceptibility genes. With the recent observation that the LQT3-associated, SCN5A-encoded cardiac sodium channel localizes in caveolae, which are known membrane microdomains whose major component in the striated muscle is caveolin-3, we hypothesized that mutations in caveolin-3 may represent a novel pathog...Keywords
This publication has 36 references indexed in Scilit:
- Localization of cardiac L-type Ca 2+ channels to a caveolar macromolecular signaling complex is required for β 2 -adrenergic regulationProceedings of the National Academy of Sciences, 2006
- Cryptic 5? splice site activation in SCN5A associated with Brugada syndromeJournal of Molecular and Cellular Cardiology, 2005
- Regulation of the Voltage-Gated Cardiac Sodium Channel Nav1.5 by Interacting ProteinsTrends in Cardiovascular Medicine, 2005
- Contribution of Sodium Channel Mutations to Bradycardia and Sinus Node Dysfunction in LQT3 FamiliesCirculation Research, 2003
- The Cardiac Sodium‐Calcium Exchanger Associates with Caveolin‐3Annals of the New York Academy of Sciences, 2002
- A β 2 Adrenergic Receptor Signaling Complex Assembled with the Ca 2+ Channel Ca v 1.2Science, 2001
- Differential Targeting of β-Adrenergic Receptor Subtypes and Adenylyl Cyclase to Cardiomyocyte CaveolaePublished by Elsevier BV ,2000
- Influence of the Genotype on the Clinical Course of the Long-QT SyndromeNew England Journal of Medicine, 1998
- Mutations in the hminK gene cause long QT syndrome and suppress lKs functionNature Genetics, 1997
- A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndromeCell, 1995