Upregulation of KCNE1 Induces QT Interval Prolongation in Patients With Chronic Heart Failure

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概要

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• 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_<Kr>) 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.

• 社団法人日本循環器学会の論文
• 2007-03-20

著者

• HISHIDA Hitoshi

  Division of Cardiology, Department of Internal Medicine, Fujita Health University School of Medicine

• 児玉 逸雄

  名古屋大学環境医学研究所循環器部門

• Hishida Hitoshi

  Division Of Cardiology Department Of Internal Medicine Fujita Health University School Of Medicine

• HONJO Haruo

  Humoral Regulation, Division of Regulation of Organ Function, Research Institute of Environmental Me

• Mori Shin

  Department Of Internal Medicine Fujita Health University School Of Medicine

• Kodama Itsuo

  東京医科歯科大学生体材料工学研究所

• YASUI Kenji

  Department of Bioinformation Analysis, Research Institute of Environmental Medicine, Nagoya Universi

• Mori Shin

  Saitama Medical Center Jichi Medical University

• Hishida H

  Department Of Cardiology Fujita Health University

• Sakuma Ichiro

  北海道大学 医学研究科循環病態内科学分野

• Sakuma I

  Graduate School Of Engineering Tokyo University

• Sakuma Ichiro

  Department Of Cardiovascular Medicine Hokkaido University School Of Medicine

• Sakuma Ichiro

  Dept. Of Pharmacology Hokkaido University Graduate School Of Medicine

• Honjou Haruo

  名古屋大学 循環器内科学

• Honjou Haruo

  Department Of Humoral Regulation Research Institute Of Environmental Medicine Nagoya University

• Honjo Haruo

  名古屋大学環境医学研究所

• Honjo Haruo

  Department Of Cardiovascular Research Research Institute Of Environmental Medicine Nagoya University

• Kamiya K

  Division Of Cardiovascular Research Reseearch Institute Of Environmental Medicine Nagoya University

• Kamiya Kaichiro

  名古屋大学環境医学研究所 循環器学

• Kamiya K

  Nagoya Univ. Nagoya Jpn

• KAMIYA Kaichiro

  Humoral Regulation Division of Regulation of Organ Function, Research Institute of Environmental Med

• Morimoto Shinichiro

  Division Of Cardiology Toyota Memorial Hospital

• Morimoto Shin-ichiro

  First Department Of Internal Medicine Shinshu University

• Morimoto Shin-ichiro

  Saitama Medical Center Jichi Medical University

• Yasui Kenji

  Department Of Bioinformation Analysis Research Institute Of Environmental Medicine Nagoya University

• Ozaki Yukio

  Division Of Cardiology Department Of Internal Medicine Fujita Health University School Of Medicine

• Watanabe Eiichi

  Division of Cardiology, Department of Internal Medicine, Fujita Health University School of Medicine

• Ozaki Yukio

  Division Of Acute Coronary Syndrome Aichi Council Of Advanced Emergency Care

• Sakuma Ichiro

  名古屋大学環境医学研究所

• Kanou Y

  Division Of Molecular And Cellular Adaptation Research Institute Of Environmental Medicine Nagoya Un

• Kanou Yasuhiko

  Department Of Genetics Research Institute Of Environmental Medicine Nagoya University

• Sakuma Ichiro

  Hokkaido University Graduate School of Medicine

• Yamaguchi Takahiro

  School of Engineering, The University of Tokyo

• Kamiya Kaichiro

  Division Of Circulation And Respiration Research Institute Of Environmental Medicine Nagoya Universi

• Yasui Kenji

  名古屋大学環境医学研究所

• Kodama Itsuo

  Circulation, Research Institute of Environmental Medicine, Nagoya University

• Yamaguchi Takahiro

  Institute of Environmental Studies, Graduate School of Frontier Science, University of Tokyo

• Sakuma Ichiro

  Institute of Environmental Studies, Graduate School of Frontier Science, University of Tokyo

• Hishida Hitoshi

  1st Department Of Internal Medicine Nagoya University School Of Medicine

• Yamaguchi Takahiro

  School Of Engineering The University Of Tokyo

• Morimoto Shinichiro

  International Cardiomyopathy Study Section Japan Research Promotion Society For Cardiovascular Disea

• Yasui Kenji

  山口大学 医学系研究科器官病態内科学循環器内科

• Morimoto Shin-ichiro

  Department Of Pathology Tokyo Women's Medical College

• Watanabe Eiichi

  Department Of Cardiology Fujita Health University

• Sakuma Ichiro

  Institute Of Environmental Studies Graduate School Of Frontier Sciences The University Of Tokyo

• Yasui Kenji

  Department Of Applied Chemistry Tokyo Metropolitan University

• Sakuma Ichiro

  Department Of Cardiovascular Medicine School Of Medicine Hokkaido University

• Sekiguchi Morie

  Dept. Of Cardiovascular Surqery The Heart Institute Of Japan Tokyo Women's Medical College

• Morimoto Shin-ichiro

  Tokyo Women's Medical College

• Morimoto Sinichiro

  Dept. Of Internal Medicine Fujita-gakuen Health University School Of Medicine

• Watanabe Eiichi

  Division Of Cardiology Department Of Internal Medicine Fujita Health University School Of Medicine

• 本荘 晴朗

  Department Of Cardiovascular Research Research Institute Of Environmental Medicine Nagoya University

• Sakuma Ichiro

  Univ. Tokyo

• Sekiguchi Morie

  Dept. Of Cardiology The Heart Institute Japan Tokyo Women's Medical College.

• Sakuma Ichiro

  Graduate School of Engineering, The University of Tokyo

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