Electrical remodeling and arrhythmias in long-QT syndrome: lessons from genetic models in mice.
Mutations in cardiac voltage-gated K+ channels cause long-QT syndrome (LQTS) and sudden death. We have created a mouse with a long-QT phenotype by overexpression of truncated K+ channels in the heart and have investigated the phenotype of these mice. These mice have long-QT phenotype, and spontaneous and inducible arrhythmias. Optical mapping of Kv1DN mice revealed spatial and temporal dispersion of repolarization that underlies the arrhythmias. Here I review our attempts to abolish arrhythmias in this model by crossbreeding with Kv4DN and Kv2DN mice or direct injection of adenoviral or adeno-associated viral vectors expressing wild-type Kv1.5 (AV-Kv1.5) into the myocardium. Our published work suggests that the viral vectors rescue the phenotype at the cellular level, while crossbreeding with Kv4DN mice attenuates the spontaneous and inducible arrhythmias.
Koren
Gideon
G
Bioelectricity Laboratory, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. gkoren@rics.bwh.harvard.edu
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006824:Hybridization, Genetic; D008133:Long QT Syndrome / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology
D015221:Potassium Channels