Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Arrhythmia/Electrophysiology
Glycine/Serine Polymorphism at Position 38 Influences KCNE1 Subunit’s Modulatory Actions on Rapid and Slow Delayed Rectifier K+ Currents
Yoshiaki YamaguchiKohki NishideMario KatoYukiko HataKoichi MizumakiKoshi KinoshitaYuki NonobeToshihide TabataTamotsu SakamotoNaoya KataokaYosuke NakataniFukiko IchidaHisashi MoriKenkichi FukurotaniHiroshi InoueNaoki Nishida
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2014 Volume 78 Issue 3 Pages 610-618

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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)

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© 2014 THE JAPANESE CIRCULATION SOCIETY
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