Long-term restitution of 4-aminopyridine-sensitive currents in Kv1DN ventricular myocytes using adeno-associated virus-mediated delivery of Kv1.5.

Overexpression of a dominant-negative truncated Kv1.1 (Kv1DN) polypeptide in the mouse heart resulted in marked attenuation of a 4-aminopyridine (4-AP)-sensitive current, I(K,slow1). We used recombinant adeno-associated virus (rAAV) as a vector for direct delivery of Kv1.5 into the mouse myocardium in order to normalize the action potential duration (APD) 6 months after injection. The injection of rAAV-Kv1.5 reconstituted the 4-AP-sensitive outward potassium currents, shortened the APD, and eliminated spontaneous early afterdepolarizations. Immunoblots detected the FL-Kv1.5 polypeptides only in rAAV-Kv1.5-infected hearts. These data demonstrate long-term expression of 4-AP-sensitive potassium currents in ventricular myocytes by gene transfer using rAAV vector encodes Kv1.5.