TY - JOUR
T1 - Circulating KCNH2 current-activating factor in patients with heart failure and ventricular tachyarrhythmia
AU - Sugiyama, Hiroki
AU - Nakamura, Kazufumi
AU - Morita, Hiroshi
AU - Akagi, Satoshi
AU - Tani, Yoshinori
AU - Katayama, Yusuke
AU - Nishii, Nobuhiro
AU - Miyoshi, Toru
AU - Nagase, Satoshi
AU - Kohno, Kunihisa
AU - Kusano, Kengo Fukushima
AU - Ohe, Tohru
AU - Kurokawa, Junko
AU - Furukawa, Tetsushi
AU - Ito, Hiroshi
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0019897
DO - 10.1371/journal.pone.0019897
M3 - Article
C2 - 21625547
AN - SCOPUS:79956288848
VL - 6
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 5
M1 - e19897
ER -