title: Tumor necrosis factor-alpha downregulates the voltage gated outward K+ current in cultured neonatal rat cardiomyocytes: a possible cause of electrical remodeling in diseased hearts.
abstract: BACKGROUND
  Inflammatory cytokines have been reported to contribute to the progression of cardiac remodeling in various heart diseases and a remarkable prolongation of the monophasic action potential duration and reductions in the expression of Kv4.2 and K+ channel-interacting protein-2 (KChIP-2) in a rat autoimmune myocarditis model have been documented. In this study, the effect of tumor necrosis factor-alpha (TNF-alpha) on cultured cardiomyocytes was evaluated, focusing on the change in the voltage-gated outward K+ current and expression of related molecules.
  
  
  RESULTS
  Cardiomyocytes isolated from 1-day-old Lewis rats were cultured for 72 h and treated with TNF-alpha (50 ng/ml) for an additional 48 h. The myocytes treated with TNF-alpha showed a 22% reduction in the peak K+ current, which consisted of a transient outward K+ current (Ito) and 1.4-fold enhancement of the cell-capacitance in comparison with the control. Among the cardiac ion channel related molecules evaluated in this study, Kv4.2 and KChIP-2 mRNA exhibited remarkable reductions (p < 0.05).
  
  
  CONCLUSIONS
  Treatment with TNF-alpha induced reductions in Ito as well as cellular hypertrophy in neonatal cultured myocytes, which indicates that TNF-alpha might play a role in promoting electrical remodeling of cardiomyocytes under inflammatory conditions.
authors.affiliation: Department of Angio-cardiology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kawada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Niwano
authors.forename: Hiroe
authors.initials: H
authors.lastname: Niwano
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yumoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Wakisaka
authors.forename: Masaru
authors.initials: M
authors.lastname: Yuge
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Kawahara
authors.forename: Tohru
authors.initials: T
authors.lastname: Izumi
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D006331:Heart Diseases / Q000473:pathology / Q000503:physiopathology; D006984:Hypertrophy / Q000139:chemically induced / Q000473:pathology; D051605:Kv Channel-Interacting Proteins / Q000187:drug effects* / Q000235:genetics; D009205:Myocarditis / Q000276:immunology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011188:Potassium / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D051672:Shal Potassium Channels / Q000187:drug effects* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C496758:Kcnip2 protein, rat; D051605:Kv Channel-Interacting Proteins; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051672:Shal Potassium Channels; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D011188:Potassium