Glycine/Serine Polymorphism at Position 38 Influences KCNE1 Subunit's Modulatory Actions on Rapid and Slow Delayed Rectifier K⁺ Currents 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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<b><i>Background:</i></b> <i>KCNE1</i> encodes a modulator of KCNH2 and KCNQ1 delayed rectifier K<sup>+</sup> current channels. <i>KCNE1</i> mutations might cause long QT syndrome (LQTS) by impairing KCNE1 subunit’s modulatory actions on these channels. There are major and minor polymorphismic <i>KCNE1</i> variants whose 38<sup>th</sup> 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<sup>+</sup> channels’ function is unclear. <b><i>Methods and Results:</i></b> Patch-clamp recordings were obtained from human embryonic kidney -293T cells. KCNH2 channel current density in <i>KCNE1(38S)</i>-transfected cells was smaller than that in <i>KCNE1(38G)</i>-transfected cells by 34%. The voltage-sensitivity of the KCNQ1 channel current in <i>KCNE1(38S)</i>-transfected cells was lowered compared to that in <i>KCNE1(38G)</i>-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 <i>KCNE1(38G)</i>-transfected cells and cells transfected with both <i>KCNE1(38G)</i> and <i>KCNE1(38S)</i>. Moreover, the KCNH2 channel current in <i>KCNE1(38S)</i>-transfected cells was more susceptible to E4031, a QT prolonging drug and a condition with hypokalemia, than that in <i>KCNE1(38G)</i>-transfected cells. <b><i>Conclusions:</i></b> Homozygous inheritance of <i>KCNE1(38S)</i> might cause a mild reduction of the delayed rectifier K<sup>+</sup> currents and might thereby increase an arrhythmogenic potential particularly in the presence of QT prolonging factors. By contrast, heterozygous inheritance of <i>KCNE1(38G)</i> and <i>KCNE1(38S)</i> might not affect the K<sup>+</sup> currents significantly.  (<i>Circ J</i> 2014; <b>78:</b> 610–618)<br>


  • Circulation Journal

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

    The Japanese Circulation Society


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