Overexpression of a truncated Kv1.1 channel transgene in the heart (KvlDN) resulted in mice with a prolonged action potential duration due to marked attenuation of a rapidly activating, slowly inactivating potassium current (IK,slow1) in ventricular myocytes. Optical mapping and programmed electrical stimulation revealed inducible ventricular tachycardia due to spatial dispersion of repolarization and refractoriness. Here we show that a delayed rectifier with slower inactivation kinetics (IK,slow2) was selectively upregulated in KvlDN cardiocytes. This electrical remodeling was spatially restricted to myocytes derived from the apex of the left ventricle. Biophysical and pharmacological studies of IK,slow2 indicate that it resembles Kv2-encoded currents. Northern blot analyses and real-time PCR revealed upregulation of Kv2.1 transcript in KvlDN mice. Crossbreeding of KvlDN mice with mice expressing a truncated Kv2.1 polypeptide (Kv2DN) eliminated IK,slow2. In summary, our data indicate that the spatially restrictive upregulation of Kv2.1-encoded currents underlies the increased dispersion of the repolarization observed in KvlDN mice.
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|Issue number||2 53-2|
|State||Published - Feb 1 2003|
- Cardiac arrhythmia
- Electrophysiology8potassium channels
- Long QT syndrome