PMID- 17384445
OWN - NLM
STAT- MEDLINE
DCOM- 20070605
LR  - 20190819
IS  - 1346-9843 (Print)
IS  - 1346-9843 (Linking)
VI  - 71
IP  - 4
DP  - 2007 Apr
TI  - Upregulation of KCNE1 induces QT interval prolongation in patients with chronic 
      heart failure.
PG  - 471-8
AB  - BACKGROUND: Prolongation of the action potential duration (APD) is observed in 
      ventricular myocytes isolated from the failing heart. The rapid component (I(Kr)) 
      and the slow component (I(Ks)) of the delayed-rectifier potassium current (I(K)) 
      are major determinants of the APD, but less information is available on the 
      genomic modulation of I(K) in the remodeled human heart. The aim of the current 
      study was to examine the relationship between I(K) transcripts and QT interval in 
      surface electrocardiogram in patients with chronic heart failure (CHF). METHODS 
      AND RESULTS: Total RNA was extracted from right ventricle endomyocardial biopsy 
      samples in 21 CHF patients (age: 53+/-4 years, mean +/- SEM). The KCNH2 and KCNQ1 
      levels did not differ significantly between controls (New York Heart Association 
      (NYHA) I, n=10) and CHF patients (NYHA II or III, n=11), whereas the KCNE1 level 
      was significantly higher in CHF patients than in controls (relative mRNA levels 
      normalized to GAPDH expression: 6.16+/-0.31 vs 7.70+/-0.46, p<0.05). The 
      KCNE1/KCNQ1 ratio was higher in CHF patients than in controls (0.92+/-0.02 vs 
      1.06+/-0.05, p<0.05) and the KCNE1-KCNQ1 ratio was positively correlated with QT 
      interval (r=0.70, p<0.05). Increasing the KCNE1 concentration caused a shift in 
      activation voltage and slowed the activation kinetics of the KCNE1-KCNQ1 currents 
      expressed in Xenopus oocytes. Prolongation of the APD and decrease in I(Ks) with 
      increasing the amount of KCNE1 concentration were well predicted in a computer 
      simulation. CONCLUSIONS: In mild-to-moderate CHF patients, the relative abundance 
      of KCNE1 compared to KCNQ1 genes, at least in part, might contribute to the 
      preferential prolongation of QT interval through reducing the net outward current 
      during the plateau of the action potential.
FAU - Watanabe, Eiichi
AU  - Watanabe E
AD  - Division of Cardiology, Department of Internal Medicine, Fujita Health University 
      School of Medicine, Toyoake.
FAU - Yasui, Kenji
AU  - Yasui K
FAU - Kamiya, Kaichiro
AU  - Kamiya K
FAU - Yamaguchi, Takahiro
AU  - Yamaguchi T
FAU - Sakuma, Ichiro
AU  - Sakuma I
FAU - Honjo, Haruo
AU  - Honjo H
FAU - Ozaki, Yukio
AU  - Ozaki Y
FAU - Morimoto, Shinichiro
AU  - Morimoto S
FAU - Hishida, Hitoshi
AU  - Hishida H
FAU - Kodama, Itsuo
AU  - Kodama I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Circ J
JT  - Circulation journal : official journal of the Japanese Circulation Society
JID - 101137683
RN  - 0 (Delayed Rectifier Potassium Channels)
RN  - 0 (ERG1 Potassium Channel)
RN  - 0 (Ether-A-Go-Go Potassium Channels)
RN  - 0 (KCNE1 protein, human)
RN  - 0 (KCNH2 protein, human)
RN  - 0 (KCNQ1 Potassium Channel)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Action Potentials/physiology
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Cardiac Output, Low/genetics/*metabolism/physiopathology
MH  - Chronic Disease
MH  - Delayed Rectifier Potassium Channels/genetics/metabolism
MH  - ERG1 Potassium Channel
MH  - *Electrocardiography
MH  - Ether-A-Go-Go Potassium Channels/genetics/metabolism
MH  - Female
MH  - Heart Ventricles/metabolism
MH  - Humans
MH  - KCNQ1 Potassium Channel/genetics/metabolism
MH  - Long QT Syndrome/genetics/metabolism
MH  - Male
MH  - Middle Aged
MH  - Myocytes, Cardiac/metabolism/pathology
MH  - Oocytes/cytology/metabolism
MH  - Potassium Channels, Voltage-Gated/genetics/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Up-Regulation/genetics/*physiology
MH  - Xenopus laevis
EDAT- 2007/03/27 09:00
MHDA- 2007/06/06 09:00
CRDT- 2007/03/27 09:00
PHST- 2007/03/27 09:00 [pubmed]
PHST- 2007/06/06 09:00 [medline]
PHST- 2007/03/27 09:00 [entrez]
AID - JST.JSTAGE/circj/71.471 [pii]
AID - 10.1253/circj.71.471 [doi]
PST - ppublish
SO  - Circ J. 2007 Apr;71(4):471-8. doi: 10.1253/circj.71.471.