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PMID:10843886

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Citation

Jeron, A, Mitchell, GF, Zhou, J, Murata, M, London, B, Buckett, P, Wiviott, SD and Koren, G (2000) Inducible polymorphic ventricular tachyarrhythmias in a transgenic mouse model with a long Q-T phenotype. Am. J. Physiol. Heart Circ. Physiol. 278:H1891-8

Abstract

We created a mouse model with a prolonged Q-T interval and spontaneous arrhythmias by overexpressing the NH(2) terminus 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.

Links

PubMed

Keywords

Action Potentials; Animals; Cardiac Pacing, Artificial; Electrocardiography; Electrophysiology; Long QT Syndrome/genetics; Mice; Mice, Transgenic/genetics; Phenotype; Reaction Time; Reference Values; Tachycardia, Ventricular/etiology; Tachycardia, Ventricular/genetics; Tachycardia, Ventricular/physiopathology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:KCNH2

involved_in

GO:0086091: regulation of heart rate by cardiac conduction

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KCNH2

involved_in

GO:0060307: regulation of ventricular cardiac muscle cell membrane repolarization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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