Inducible polymorphic ventricular tachyarrhythmias in a transgenic mouse model with a long Q-T phenotype

Andreas Jeron; Gary F Mitchell; Jun Zhou; Mitsunobu Murata; Barry London; Peter Buckett; Stephen D Wiviott; Gideon Koren

doi:10.1152/ajpheart.2000.278.6.H1891

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Inducible polymorphic ventricular tachyarrhythmias in a transgenic mouse model with a long Q-T phenotype

Journal article

Peer reviewed

Inducible polymorphic ventricular tachyarrhythmias in a transgenic mouse model with a long Q-T phenotype

Andreas Jeron, Gary F Mitchell, Jun Zhou, Mitsunobu Murata, Barry London, Peter Buckett, Stephen D Wiviott and Gideon Koren

American journal of physiology. Heart and circulatory physiology, Vol.278(6), pp.H1891-H1898

06/01/2000

DOI: 10.1152/ajpheart.2000.278.6.H1891

PMID: 10843886

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Abstract

We created a mouse model with a prolonged Q-T interval and spontaneous arrhythmias by overexpressing the NH2terminus and first transmembrane segment ( Kv1.1N206Tag) of a delayed rectifier potassium channel (LQT+/ − mouse). Analyses were performed using whole cell recordings of cardiac myocytes, surface electrocardiography, and programmed electrical stimulation. Action potential duration (APD) was prolonged to the same extent and was more highly variable in myocytes derived from LQT+/ − and LQT+/+ mice than in myocytes derived from wild-type (WT) FVB mice. Under ketamine anesthesia, the Q-T interval of both LQT+/+ and LQT+/ − mice was comparably prolonged versus that of WT mice. Stimulation of the right ventricle using an intracardiac catheter induced polymorphic ventricular tachyarrhythmias in 50% of the LQT+/ − mice and 36% of the LQT+/+ mice, whereas polymorphic ventricular tachyarrhythmias were not inducible in WT mice. The analyses of LQT+/ − and LQT+/+ mice indicate that prolongation of the Q-T interval in LQT mice is associated with prolonged APD, increased dispersion of APD among cardiocytes, and inducibility of polymorphic ventricular tachycardia, providing the substrate for spontaneous arrhythmias in these animals.

Details

Title: Subtitle: Inducible polymorphic ventricular tachyarrhythmias in a transgenic mouse model with a long Q-T phenotype
Creators: Andreas Jeron - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and
Gary F Mitchell - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and
Jun Zhou - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and
Mitsunobu Murata - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and
Barry London - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213
Peter Buckett - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and
Stephen D Wiviott - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and
Gideon Koren - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and
Resource Type: Journal article
Publication Details: American journal of physiology. Heart and circulatory physiology, Vol.278(6), pp.H1891-H1898
DOI: 10.1152/ajpheart.2000.278.6.H1891
PMID: 10843886
ISSN: 0363-6135
eISSN: 1522-1539
Language: English
Date published: 06/01/2000
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984025562102771

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