Publications [#112900] of G Vann V. Bennett

Papers Published

1. PJ Mohler, JJ Schott, AO Gramolini, KW Dilly, S Guatimosim, WH duBell, LS Song, K Haurogné, F Kyndt, ME Ali, TB Rogers, WJ Lederer, D Escande, H Le Marec, V Bennett, Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death., Nature, vol. 421 no. 6923 (February, 2003), pp. 634-9, ISSN 0028-0836 [doi]
   (last updated on 2013/05/16)

   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 syndrome. 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 adapters, 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.

   Keywords:
   Action Potentials • Animals • Ankyrins • Bradycardia • Calcium Channels • Calcium Signaling • Death, Sudden, Cardiac • Electrocardiography • Female • Heart • Heart Rate • Heterozygote • Humans • Inositol 1,4,5-Trisphosphate Receptors • Long QT Syndrome • Male • Mice • Mutation • Myocardium • Patch-Clamp Techniques • Pedigree • Phenotype • Protein Binding • Receptors, Cytoplasmic and Nuclear • Sodium-Calcium Exchanger • Sodium-Potassium-Exchanging ATPase • classification • complications • etiology* • genetics • genetics* • metabolism • pathology • physiology • physiopathology