心筋細胞活動電位シミュレーションを用いたQT延長メカニズムの検討

• 山口 喬弘

  東京大学大学院新領域創成科学研究科

• 荒船 龍彦

  東京大学大学院新領域創成科学研究科

• 佐久間 一郎

  東京大学大学院新領域創成科学研究科

• 大内 克洋

  東京医科歯科大学生体材料工学研究所

• 柴田 仁太郎

  東京都保健医療公社大久保病院

• 本荘 晴朗

  名古屋大学環境医学研究所

• 神谷 香一郎

  名古屋大学環境医学研究所

• 児玉 逸雄

  名古屋大学環境医学研究所

書誌事項

タイトル別名

• Analysis of QT Prolongation Using Cardiac Action Potential Simulation
• シンキン サイボウ カツドウ デンイ シミュレーション オ モチイタ QT エンチョウ メカニズム ノ ケントウ

抄録

In heart failure, QT interval and action potential duration (APD) is prolonged and I_Ks, a slow component of delayed rectifier potassium current, decreases. We have reported that the KCNE1 gene, coding I_Ks channel, increases and QT interval is prolonged in patients with heart failure. Since it is known that increasing KCNE1 increases the maximum conductance of the I_Ks channel, the mechanism of APD prolongation is not explained by the over expression of KCNE1. In this study, we construct a cardiac membrane action potential simulation model based on the experimental data from oocytes expression to investigate the relationship between the increase of KCNE1 and APD. In the experiment of oocyte expression, 1 ng and 5 ng of KCNE1 were co-injected with 5 ng of KCNQ1. Expressed currents were recorded 1-2 days after injection by the double-microelectrode voltage clamp method at 35 degrees centigrade. Maximum I_Ks conductance and relationships between time constants, maximum activation parameter and membrane potential were obtained from fitting functions describing I_Ks channel properties in the Luo-Rudy model to experimental results with the Nelder-Mead simplex method. In simulations, APD was prolonged by increasing the co-injected amount of KCNE1. APD at 5 ng KCNE1 was 183 ms, which is 3.4% longer than that at 1 ng KCNE1 (APD=177 ms). This study shows that increasing the KCNE1 expression level makes maximum I_Ks conductance increase and I_Ks channel open slowly and I_Ks conductance decrease according to the APD time scale. Therefore increasing the KCNE1 expression level may prolong APD with this mechanism. This method of constructing a simulation model based on experiments helps to explain the relationship between KCNE1 expression ratio and QT interval prolongation.

収録刊行物

• 生体医工学

  生体医工学 43 (1), 43-49, 2005

  公益社団法人 日本生体医工学会

キーワード

• QT interval prolongation
• remodeling
• <i>I</i>_Ks current
• KCNE1
• Luo-Rudy model

詳細情報

• CRID: 1390282680244394496
• NII論文ID: 110004012634
• NII論文ID: 130004493912
• NII書誌ID: AA11633569
• DOI: 10.11239/jsmbe.43.43
• ISSN: 18814379
• ISSN: 1347443X
• NDL書誌ID: 7329411
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7329411
• Web Site: https://search.jamas.or.jp/link/ui/2005235080
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • NDL
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可