Direct myocardial injection of adenoviral vectors expressing wild-type Kv1.5 in mice with a long QT phenotype shortened the action potential duration and QT interval at 3-10 days.
Does direct injection of adenoviral vectors expressing wild-type Kv1.5 normalize action potential duration and shorten QT interval in transgenic mice with a long QT phenotype?
In vivo gene transfer of Kv1.5 successfully normalizes action potential duration and shortens the QT interval in a mouse model of long QT syndrome.
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.
Brunner et al. (Tue,) conducted a other in Long QT syndrome (LQTS). Adenoviral vectors expressing wild-type Kv1.5 (AV-Kv1.5) was evaluated on Electrophysiology in isolated cardiomyocytes, surface ECG, programmed stimulation of the right ventricle, and in vivo optical mapping. Direct myocardial injection of adenoviral vectors expressing wild-type Kv1.5 in mice with a long QT phenotype shortened the action potential duration and QT interval at 3-10 days.