Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death

Peter J. Mohler, Jean-Jacques Schott, Anthony O. Gramolini, Keith W. Dilly, Silvia Guatimosim, William H. duBell, Long-Sheng Song, Karine Haurogné, Florence Kyndt, Mervat E. Ali, Terry B. Rogers, W. J. Lederer, Denis Escande, Herve Le Marec and Vann Bennett ()
Additional contact information
Peter J. Mohler: Duke University Medical Center
Jean-Jacques Schott: Hôspital G&R Laennec
Anthony O. Gramolini: Duke University Medical Center
Keith W. Dilly: University of Maryland Biotechnology Institute
Silvia Guatimosim: University of Maryland Biotechnology Institute
William H. duBell: University of Maryland School of Medicine
Long-Sheng Song: University of Maryland Biotechnology Institute
Karine Haurogné: Hôspital G&R Laennec
Florence Kyndt: Hôspital G&R Laennec
Mervat E. Ali: Duke University Medical Center
Terry B. Rogers: University of Maryland School of Medicine
W. J. Lederer: University of Maryland Biotechnology Institute
Denis Escande: Hôspital G&R Laennec
Herve Le Marec: Hôspital G&R Laennec
Vann Bennett: Duke University Medical Center

Nature, 2003, vol. 421, issue 6923, 634-639

Abstract: Abstract Mutations in ion channels involved in the generation and termination of action potentials constitute a family of molecular defects that underlie fatal cardiac arrhythmias in inherited long-QT syndrome1. We report here that a loss-of-function (E1425G) mutation in ankyrin-B (also known as ankyrin 2), a member of a family of versatile membrane adapters2, causes dominantly inherited type 4 long-QT cardiac arrhythmia in humans. Mice heterozygous for a null mutation in ankyrin-B are haploinsufficient and display arrhythmia similar to humans. Mutation of ankyrin-B results in disruption in the cellular organization of the sodium pump, the sodium/calcium exchanger, and inositol-1,4,5-trisphosphate receptors (all ankyrin-B-binding proteins), which reduces the targeting of these proteins to the transverse tubules as well as reducing overall protein level. Ankyrin-B mutation also leads to altered Ca2+ signalling in adult cardiomyocytes that results in extrasystoles, and provides a rationale for the arrhythmia. Thus, we identify a new mechanism for cardiac arrhythmia due to abnormal coordination of multiple functionally related ion channels and transporters.

Date: 2003
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature01335 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:421:y:2003:i:6923:d:10.1038_nature01335

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01335

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().