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.
Kodirov
S A
SA
Bioelectricity Laboratory, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Brunner
M
M
Busconi
L
L
Koren
G
G
D015761:4-Aminopyridine / Q000494:pharmacology*; D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics*; D004594:Electrophysiology / Q000379:methods*; D018014:Gene Transfer Techniques; D005799:Genes, Dominant; D006352:Heart Ventricles / Q000166:cytology; D051662:Kv1.1 Potassium Channel; D051666:Kv1.5 Potassium Channel; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D013995:Time; D016276:Ventricular Function
C496947:Kcna1 protein, mouse; C496982:Kcna5 protein, mouse; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel; D015761:4-Aminopyridine; D011188:Potassium