Electrical remodeling and arrhythmias in long-QT syndrome: Lessons from genetic models in mice

Mutations in cardiac voltage-gated K⁺ channels cause long-OT 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.