title: KCNE2 protein is expressed in ventricles of different species, and changes in its expression contribute to electrical remodeling in diseased hearts.
abstract: BACKGROUND
  Mutations in KCNE2 have been linked to long-QT syndrome (LQT6), yet KCNE2 protein expression in the ventricle and its functional role in native channels are not clear.
  
  
  RESULTS
  We detected KCNE2 protein in human, dog, and rat ventricles in Western blot experiments. Immunocytochemistry confirmed KCNE2 protein expression in ventricular myocytes. To explore the functional role of KCNE2, we studied how its expression was altered in 2 models of cardiac pathology and whether these alterations could help explain observed changes in the function of native channels, for which KCNE2 is a putative auxiliary (beta) subunit. In canine ventricle injured by coronary microembolizations, the rapid delayed rectifier current (I(Kr)) density was increased. Although the protein level of ERG (I(Kr) pore-forming, alpha, subunit) was not altered, the KCNE2 protein level was markedly reduced. These data are consistent with the effect of heterologously expressed KCNE2 on ERG and suggest that in canine ventricle, KCNE2 may associate with ERG and suppress its current amplitude. In aging rat ventricle, the pacemaker current (I(f)) density was increased. There was a significant increase in the KCNE2 protein level, whereas changes in the alpha-subunit (HCN2) were not significant. These data are consistent with the effect of heterologously expressed KCNE2 on HCN2 and suggest that in aging rat ventricle, KCNE2 may associate with HCN2 and enhance its current amplitude.
  
  
  CONCLUSIONS
  KCNE2 protein is expressed in ventricles, and it can play diverse roles in ventricular electrical activity under (patho)physiological conditions.
authors.affiliation: Department of Physiology, Virginia Commonwealth UniversityRichmond, VA 23298, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tang
authors.forename: Henry F
authors.initials: HF
authors.lastname: Clemo
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Dana
authors.initials: D
authors.lastname: Holwitt
authors.forename: Vigneshwar
authors.initials: V
authors.lastname: Kasirajan
authors.forename: Amber L
authors.initials: AL
authors.lastname: Pond
authors.forename: Erich
authors.initials: E
authors.lastname: Wettwer
authors.forename: Gea-Ny
authors.initials: GN
authors.lastname: Tseng
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004285:Dogs; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006329:Heart Conduction System / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000378:metabolism; D017136:Ion Transport; D008133:Long QT Syndrome / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D014162:Transfection; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C578710:HCN2 protein, human; C578712:Hcn2 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D046911:Macromolecular Substances; D009124:Muscle Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; C059983:potassium channel protein I(sk); D011188:Potassium