title: Epigallocatechin-3-gallate modulates arrhythmogenic activity and calcium homeostasis of left atrium.
abstract: BACKGROUND
  Atrial fibrillation (AF) is the commonest sustained arrhythmia, and increases the risk of stroke, heart failure, and mortality. Calcium (Ca2+) overload and oxidative stress are thought to participate in the pathogenesis of AF. Epigallocatechin-3-gallate (EGCG) has an antioxidative effect and been shown to be beneficial in promoting cardiovascular health. However, it is not clear if EGCG directly modulates the electrophysiological characteristics and Ca2+homeostasis of the left atrium (LA).
  
  
  RESULTS
  Conventional microelectrodes, whole-cell patch-clamp, and Fluo-3 fluorometric ratio technique were performed using the isolated rabbit LA preparations or isolated single LA cardiomyocytes before and after EGCG treatment. EGCG (0.01, 0.1, 1, and 10μM) which concentration-dependently decreased the APD20by 13±8%, 25±5%, 31±6%, and 37±5%, APD50by 9±8%, 22±6%, 32±7%, and 40±4%, and APD90by 2±12%, 9±8%, 24±10%, and 34±5% in LA preparations. EGCG (0.1μM) decreased the late sodium (Na+) current, L-type Ca2+current, nickel-sensitive Na+-Ca2+exchanger current, and transient outward current, but did not change the Na+current and ultra-rapid delayed rectifier potassium current in LA cardiomyocytes. EGCG decreased intracellular Ca2+transient and sarcoplasmic reticulum Ca2+content in LA cardiomyocytes. Furthermore, EGCG decreased isoproterenol (ISO, 1μM)-induced burst firing. KT5823 (1μM) or KN93 (1μM) decreased the incidences of ISO-induced LA burst firing, which became lower with EGCG treatment. H89 (10μM) and KN92 (1μM) did not suppress the incidence of ISO-induced LA burst firing. However, EGCG decreased the incidences of ISO-induced LA burst firing in the presence of H89 or KN92.
  
  
  CONCLUSIONS
  EGCG directly regulates LA electrophysiological characteristics and Ca2+homeostasis, and suppresses ISO-induced atrial arrhythmogenesis through inhibiting Ca2+/calmodulin or cGMP-dependent protein kinases.
authors.affiliation: Biomedical Engineering Program, Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan.
authors.forename: Jun-Hei
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Shih-Lin
authors.initials: SL
authors.lastname: Chang
authors.affiliation: Biomedical Engineering Program, Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan.
authors.forename: Po-Da
authors.initials: PD
authors.lastname: Hong
authors.affiliation: Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ping-Nan
authors.initials: PN
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Electronic address: jhon10298@gmail.com.
authors.forename: Chih-Hsueng
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; Division of Cardiology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei City, Taiwan. Electronic address: yolu59@yahoo.com.tw.
authors.forename: Yen-Yu
authors.initials: YY
authors.lastname: Lu
authors.affiliation: Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan; Department of Medical, Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei, Taiwan. Electronic address: bme02@mail.ndmctsghed.edu.tw.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D016279:Atrial Function, Left / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D006325:Heart Atria / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D011817:Rabbits
chemical_list: D002392:Catechin; C045651:epigallocatechin gallate; D002118:Calcium
keywords: Atrial fibrillation; Calcium homeostasis; Epigallocatechin-3-gallate; Left atrium