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

Yoshiaki Yamaguchi; Kohki Nishide; Mario Kato; Yukiko Hata; Koichi Mizumaki; Koshi Kinoshita; Yuki Nonobe; Toshihide Tabata; Tamotsu Sakamoto; Naoya Kataoka; Yosuke Nakatani; Fukiko Ichida; Hisashi Mori; Kenkichi Fukurotani; Hiroshi Inoue; Naoki Nishida

doi:10.1253/circj.CJ-13-1126

Arrhythmia/Electrophysiology

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

Yoshiaki Yamaguchi, Kohki Nishide, Mario Kato, Yukiko Hata, Koichi Mizumaki, Koshi Kinoshita, Yuki Nonobe, Toshihide Tabata, Tamotsu Sakamoto, Naoya Kataoka, Yosuke Nakatani, Fukiko Ichida, Hisashi Mori, Kenkichi Fukurotani, Hiroshi Inoue, Naoki Nishida

Author information

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

Keywords: Arrhythmia, Human ether-à-go-go-related gene channel, K_V7.1, K_V11.1, Mink

JOURNAL FREE ACCESS

2014 Volume 78 Issue 3 Pages 610-618

DOI https://doi.org/10.1253/circj.CJ-13-1126

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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 38^th 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)

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