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

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  • Yamaguchi Yoshiaki
    Second Department of Internal Medicine, University of Toyama
  • Nishide Kohki
    Laboratory for Neural Information Technology, Graduate School of Sciences and Engineering, University of Toyama
  • Kato Mario
    Laboratory for Neural Information Technology, Graduate School of Sciences and Engineering, University of Toyama
  • Hata Yukiko
    Department of Legal Medicine, University of Toyama
  • Mizumaki Koichi
    Clinical Research and Ethics Center, University of Toyama
  • Kinoshita Koshi
    Department of Legal Medicine, University of Toyama
  • Nonobe Yuki
    Laboratory for Neural Information Technology, Graduate School of Sciences and Engineering, University of Toyama
  • Tabata Toshihide
    Laboratory for Neural Information Technology, Graduate School of Sciences and Engineering, University of Toyama
  • Sakamoto Tamotsu
    Second Department of Internal Medicine, University of Toyama
  • Kataoka Naoya
    Second Department of Internal Medicine, University of Toyama
  • Nakatani Yosuke
    Second Department of Internal Medicine, University of Toyama
  • Ichida Fukiko
    Department of Pediatrics, University of Toyama
  • Mori Hisashi
    Department of Molecular Neurosciences, University of Toyama
  • Fukurotani Kenkichi
    Laboratory for Neural Information Technology, Graduate School of Sciences and Engineering, University of Toyama
  • Inoue Hiroshi
    Second Department of Internal Medicine, University of Toyama
  • Nishida Naoki
    Department of Legal Medicine, University of Toyama

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

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Abstract

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>

Journal

  • Circulation Journal

    Circulation Journal 78 (3), 610-618, 2014

    The Japanese Circulation Society

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