title: Over-expression of Kv1.5 in rat cardiomyocytes extremely shortens the duration of the action potential and causes rapid excitation.
abstract: BACKGROUND
  Genetically abnormal action potential duration (APD) can be a cause of arrhythmias that include long and short QT interval syndrome.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the arrhythmogenic effect of short QT syndrome induced by the over-expression of Kv1.5 in rat.
  
  
  METHODS
  From Sprague-Dawley rats on fetal days 18-19, cardiomyocytes were excised and cultured with and without transfection with the Kv-1.5 gene using an adenovirus vector. The expression of Kv1.5 was proven by immunohistochemistry and Western blot analysis. In the culture dish and in the whole cells, the electrical activities were recorded using the whole-cell patch-clamp technique and the effects of 4-AP and verapamil were tested.
  
  
  RESULTS
  After transfection with Kv1.5 for 12h, immunohistochemical staining and Western blot analysis were positive for Kv1.5 while they were negative in the control transfected with only Lac-Z. In the culture dish, the myocytes showed spontaneous beating at 115beats/min (bpm) just prior to the transfection with Kv1.5 and increased to 367bpm at 24h. The control myocytes showed stable beating rates during culturing. 4-AP at 200microM slowed down the rate and verapamil abolished the beating. In the whole cells, the maximal resting membrane potential was slightly depolarized and APD was extremely abbreviated both at 50% and 90% of repolarization compared with those of the control. Rapid spontaneous activities were found in a single myocyte with Kv1.5 transfection and 4-AP slowed down the frequency of the activities with a reversal of the shortened APD.
  
  
  CONCLUSIONS
  The over-expression of Kv1.5 induced short APD and triggered activities in rat cardiomyocytes. This model can be used to study the arrhythmogenic substrate of short QT syndrome.
authors.affiliation: Division of Cardiology, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Katsuharu
authors.initials: K
authors.lastname: Hatada
authors.forename: Naoki
authors.initials: N
authors.lastname: Naito
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Aizawa
authors.forename: Masaomi
authors.initials: M
authors.lastname: Chinushi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nawa
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000200:Action Potentials; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051666:Kv1.5 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013577:Syndrome; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D051666:Kv1.5 Potassium Channel; D014700:Verapamil