Title: Abrupt rate accelerations or premature beats cause life-threatening arrhythmias in mice with long-QT3 syndrome
Authors: Nuyens, Dieter ×
Stengl, M
Dugarmaa, S
Rossenbacker, Tom
Compernolle, Veerle
Rudy, Y
Smits, J F
Flameng, Willem
Clancy, CE
Moons, Lieve
Vos, M
Dewerchin, Mieke
Benndorf, K
Collen, Desire
Carmeliet, Edward
Carmeliet, Peter #
Issue Date: Sep-2001
Publisher: Nature Pub. Co.
Series Title: Nature Medicine vol:7 issue:9 pages:1021-1027
Abstract: Deletion of amino-acid residues 1505-1507 (KPQ) in the cardiac SCN5A Na(+) channel causes autosomal dominant prolongation of the electrocardiographic QT interval (long-QT syndrome type 3 or LQT3). Excessive prolongation of the action potential at low heart rates predisposes individuals with LQT3 to fatal arrhythmias, typically at rest or during sleep. Here we report that mice heterozygous for a knock-in KPQ-deletion (SCN5A(Delta/+)) show the essential LQT3 features and spontaneously develop life-threatening polymorphous ventricular arrhythmias. Unexpectedly, sudden accelerations in heart rate or premature beats caused lengthening of the action potential with early afterdepolarization and triggered arrhythmias in Scn5a(Delta/+) mice. Adrenergic agonists normalized the response to rate acceleration in vitro and suppressed arrhythmias upon premature stimulation in vivo. These results show the possible risk of sudden heart-rate accelerations. The Scn5a(Delta/+) mouse with its predisposition for pacing-induced arrhythmia might be useful for the development of new treatments for the LQT3 syndrome.
ISSN: 1078-8956
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Experimental Cardiac Surgery (-)
Faculty of Medicine - miscellaneous
Laboratory of Neuronal Communication
Vesalius Research Centre (-)
Animal Physiology and Neurobiology Section - miscellaneous
Physiology Section (-)
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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