Glycine/Serine Polymorphism at Position 38 Influences KCNE1 Subunit's Modulatory Actions on Rapid and Slow Delayed Rectifier K⁺ Currents

DOI DOI DOI Web Site Web Site ほか5件をすべて表示 一部だけ表示 被引用文献4件 参考文献40件 オープンアクセス
  • Tabata Toshihide
    Laboratory for Neural Information Technology, Graduate School of Sciences and Engineering, University of Toyama
  • Yamaguchi Yoshiaki
    Second Department of Internal Medicine, University of Toyama
  • Hata Yukiko
    Department of Legal Medicine, University of Toyama
  • Ichida Fukiko
    Department of Pediatrics, University of Toyama
  • Mori Hisashi
    Department of Molecular Neurosciences, University of Toyama

書誌事項

タイトル別名
  • Modification of <i>KCNH2</i>-Encoded Cardiac Potassium Channels by KCNE1 Polymorphism
  • Glycine/Serine Polymorphism at Position 38 Influences KCNE1 Subunit’s Modulatory Actions on Rapid and Slow Delayed Rectifier K<sup>+</sup> Currents
  • – Reply –

この論文をさがす

説明

Background: KCNE1 encodes a modulator of KCNH2 and KCNQ1 delayed rectifier K+ current channels. KCNE1 mutations might cause long QT syndrome (LQTS) by impairing KCNE1 subunit’s modulatory actions on these channels. There are major and minor polymorphismic KCNE1 variants whose 38th amino acids are glycine and serine [KCNE1(38G) and KCNE1(38S) subunits], respectively. Despite its frequent occurrence, the influence of this polymorphism on the K+ channels’ function is unclear. Methods and Results: Patch-clamp recordings were obtained from human embryonic kidney -293T cells. KCNH2 channel current density in KCNE1(38S)-transfected cells was smaller than that in KCNE1(38G)-transfected cells by 34%. The voltage-sensitivity of the KCNQ1 channel current in KCNE1(38S)-transfected cells was lowered compared to that in KCNE1(38G)-transfected cells, with a +13mV shift in the half-maximal activation voltage. KCNH2 channel current density or KCNQ1 channel voltage-sensitivity was not different between KCNE1(38G)-transfected cells and cells transfected with both KCNE1(38G) and KCNE1(38S). Moreover, the KCNH2 channel current in KCNE1(38S)-transfected cells was more susceptible to E4031, a QT prolonging drug and a condition with hypokalemia, than that in KCNE1(38G)-transfected cells. Conclusions: Homozygous inheritance of KCNE1(38S) might cause a mild reduction of the delayed rectifier K+ currents and might thereby increase an arrhythmogenic potential particularly in the presence of QT prolonging factors. By contrast, heterozygous inheritance of KCNE1(38G) and KCNE1(38S) might not affect the K+ currents significantly.  (Circ J 2014; 78: 610–618)<br>

収録刊行物

  • Circulation Journal

    Circulation Journal 78 (9), 2331-, 2014

    一般社団法人 日本循環器学会

被引用文献 (4)*注記

もっと見る

参考文献 (40)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ