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

FEBS Letters

Kodirov, S.A¹  Koren, G¹  Brunner, M¹  Busconi, L¹ 

[1] Bioelectricity Laboratory, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

关键词: Adeno-associated virus;    Delayed rectifier K+ channel;    4-Aminopyridine;    APs;    action potentials;    APD;    action potential duration;    rAAV;    recombinant adeno-associated virus;    4-AP;    4-aminopyridine;    TEA;    tetraethylammonium;    EADs;    early afterdepolarizations;    LV;    left ventricle;   

DOI  :  10.1016/S0014-5793(03)00822-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown