Circulating KCNH2 current-activating factor in patients with heart failure and ventricular tachyarrhythmia

Hiroki Sugiyama, Kazufumi Nakamura, Hiroshi Morita, Satoshi Akagi, Yoshinori Tani, Yusuke Katayama, Nobuhiro Nishii, Toru Miyoshi, Satoshi Nagase, Kunihisa Kohno, Kengo Fukushima Kusano, Tohru Ohe, Junko Kurokawa, Tetsushi Furukawa, Hiroshi Ito

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 (IKr) is recognized as the most susceptible channel in acquired long QT syndrome. Recent findings have revealed that not only suppression but also enhancement of IKr 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. Methodology/Principal Findings: We examined the effects of serum of HF patients on recombinant IKr 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 IKr tail currents compared to the serum from normal controls and HF patients without ventricular arrhythmia. Conclusions/Significance: 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.

Original languageEnglish
Article numbere19897
JournalPloS one
Volume6
Issue number5
DOIs
Publication statusPublished - May 25 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Circulating KCNH2 current-activating factor in patients with heart failure and ventricular tachyarrhythmia'. Together they form a unique fingerprint.

  • Cite this