title: Electrical remodeling and arrhythmias in long-QT syndrome: lessons from genetic models in mice.
abstract: 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.
authors.affiliation: Bioelectricity Laboratory, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. gkoren@rics.bwh.harvard.edu
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: 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
chemical_list: D015221:Potassium Channels