title: Mechanical stretch of atrial myocyte monolayer decreases sarcoplasmic reticulum calcium adenosine triphosphatase expression and increases susceptibility to repolarization alternans.
abstract: OBJECTIVE
  The purpose of this study was to investigate the effect of stretch (the major risk factor for atrial fibrillation [AF]) on spatial and temporal alternations of action potential duration (APD-ALT) and calcium transient in cultured atrial myocyte monolayer.
  
  
  BACKGROUND
  How rapid firings or premature beats trigger AF is not completely understood. Discordant repolarization alternans, characterized by simultaneous prolongation and shortening of APD in different myocardial regions, is central to the genesis of ventricular fibrillation. We hypothesized that repolarization alternans also is central to the initiation of multiple re-entry circuits and AF.
  
  
  METHODS
  Confluent HL-1 atrial myocyte monolayer with spontaneous depolarization was cultured in silicone membrane and subjected to mechanical stretch. Rapid field pacing was used to induce alternans. A high-resolution dual optical mapping system was used to record action potentials and calcium transients.
  
  
  RESULTS
  High-rate pacing induced APD-ALT and calcium transient in atrial myocyte monolayer. Mechanical stretch significantly decreased the thresholds for APD-ALT and calcium transient. Mechanical stretch decreased the expression of sarcoplasmic reticulum adenosine triphosphatase 2, and thus slower calcium reuptake kinetics, which was responsible for the susceptibility to alternans. Mechanical stretch did not alter the APD restitution kinetics. Mechanical stretch also enhanced spatially discordant alternans. Overexpression of sarcoplasmic reticulum adenosine triphosphatase 2 reversed all the effects of stretch on susceptibility to alternans. In intact atrium, mechanical stretch also enhanced discordant alternans.
  
  
  CONCLUSIONS
  Mechanical stretch increased the susceptibility to alternans in atrial myocytes, which may explain the susceptibility to AF in conditions of atrial stretch, such as mitral valvular heart disease, heart failure, and hypertension.
authors: Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Chia-Ti
authors: CT
authors: Tsai
authors: Fu-Tien
authors: FT
authors: Chiang
authors: Chuen-Den
authors: CD
authors: Tseng
authors: Chih-Chieh
authors: CC
authors: Yu
authors: Yi-Chih
authors: YC
authors: Wang
authors: Ling-Ping
authors: LP
authors: Lai
authors: Juey-Jen
authors: JJ
authors: Hwang
authors: Jiunn-Lee
authors: JL
authors: Lin
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000201:enzymology / Q000209:etiology*; D016275:Atrial Function; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003971:Diastole / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium