title: Circulating KCNH2 current-activating factor in patients with heart failure and ventricular tachyarrhythmia.
abstract: BACKGROUND
  It is estimated that approximately half of the deaths in patients with HF are sudden and that the most likely causes of sudden death are lethal ventricular tachyarrhythmias such as ventricular tachycardia (VT) or fibrillation (VF). However, the precise mechanism of ventricular tachyarrhythmias remains unknown. The KCNH2 channel conducting the delayed rectifier K(+) current (I(Kr)) is recognized as the most susceptible channel in acquired long QT syndrome. Recent findings have revealed that not only suppression but also enhancement of I(Kr) increase vulnerability to major arrhythmic events, as seen in short QT syndrome. Therefore, we investigated the existence of a circulating KCNH2 current-modifying factor in patients with HF.
  
  
  RESULTS
  We examined the effects of serum of HF patients on recombinant I(Kr) recorded from HEK 293 cells stably expressing KCNH2 by using the whole-cell patch-clamp technique. Study subjects were 14 patients with non-ischemic HF and 6 normal controls. Seven patients had a history of documented ventricular tachyarrhythmias (VT: 7 and VF: 1). Overnight treatment with 2% serum obtained from HF patients with ventricular arrhythmia resulted in a significant enhancement in the peaks of I(Kr) tail currents compared to the serum from normal controls and HF patients without ventricular arrhythmia.
  
  
  CONCLUSIONS
  Here we provide the first evidence for the presence of a circulating KCNH2 channel activator in patients with HF and ventricular tachyarrhythmias. This factor may be responsible for arhythmogenesis in patients with HF.
authors.affiliation: Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Akagi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tani
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Katayama
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishii
authors.forename: Toru
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagase
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Kohno
authors.forename: Kengo Fukushima
authors.initials: KF
authors.lastname: Kusano
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohe
authors.forename: Junko
authors.initials: J
authors.lastname: Kurokawa
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Furukawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000097:blood*; D005260:Female; D057809:HEK293 Cells; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D017180:Tachycardia, Ventricular / Q000097:blood* / Q000175:diagnosis
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D011188:Potassium