title: Glycine/Serine polymorphism at position 38 influences KCNE1 subunit's modulatory actions on rapid and slow delayed rectifier K+ currents.
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.
  
  
  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).
authors.affiliation: Second Department of Internal Medicine, University of Toyama.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Kohki
authors.initials: K
authors.lastname: Nishide
authors.forename: Mario
authors.initials: M
authors.lastname: Kato
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hata
authors.forename: Koichi
authors.initials: K
authors.lastname: Mizumaki
authors.forename: Koshi
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nonobe
authors.forename: Toshihide
authors.initials: T
authors.lastname: Tabata
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Naoya
authors.initials: N
authors.lastname: Kataoka
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Fukiko
authors.initials: F
authors.lastname: Ichida
authors.forename: Hisashi
authors.initials: H
authors.lastname: Mori
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Fukurotani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Naoki
authors.initials: N
authors.lastname: Nishida
mesh_terms: D019943:Amino Acid Substitution; D005260:Female; D005998:Glycine / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D017136:Ion Transport / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D011110:Polymorphism, Genetic; D011188:Potassium / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism
chemical_list: C489622:KCNE1 protein, human; D024642:Potassium Channels, Voltage-Gated; D012694:Serine; D011188:Potassium; D005998:Glycine