Back to Search
Start Over
In vivo gene transfer of Kv1.5 normalizes action potential duration and shortens QT interval in mice with long QT phenotype.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2003 Jul; Vol. 285 (1), pp. H194-203. - Publication Year :
- 2003
-
Abstract
- Mutations in cardiac voltage-gated K+ channels cause long QT syndrome (LQTS) and sudden death. We created a transgenic mouse with a long QT phenotype (Kv1DN) by overexpression of a truncated K+ channel in the heart and investigated whether the dominant negative effect of the transgene would be overcome by the direct injection of adenoviral vectors expressing wild-type Kv1.5 (AV-Kv1.5) into the myocardium. End points at 3-10 days included electrophysiology in isolated cardiomyocytes, surface ECG, programmed stimulation of the right ventricle, and in vivo optical mapping of action potentials and repolarization gradients in Langendorff-perfused hearts. Overexpression of Kv1.5 reconstituted a 4-aminopyridine-sensitive outward K+ current, shortened the action potential duration, eliminated early afterdepolarizations, shortened the QT interval, decreased dispersion of repolarization, and increased the heart rate. Each of these changes is consistent with a physiologically significant primary effect of adenoviral expression of Kv1.5 on ventricular repolarization of Kv1DN mice.
- Subjects :
- 4-Aminopyridine pharmacology
Action Potentials physiology
Adenoviridae genetics
Animals
Blotting, Western
Cells, Cultured
Cloning, Molecular
Electrocardiography
Electrophysiology
Gene Transfer Techniques
Kv1.5 Potassium Channel
Long QT Syndrome genetics
Mice
Muscle Cells drug effects
Muscle Cells metabolism
Myocardium cytology
Myocardium metabolism
Patch-Clamp Techniques
Phenotype
Potassium Channel Blockers pharmacology
Potassium Channels drug effects
Long QT Syndrome physiopathology
Potassium Channels genetics
Potassium Channels, Voltage-Gated
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 285
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 12793978
- Full Text :
- https://doi.org/10.1152/ajpheart.00971.2002