title: Transfection by eukaryotic expression vector pcDNA3-HERG inhibits the cultured neonatal rabbit ventricular myocyte hypertrophy induced by phenylephrine.
abstract: OBJECTIVE
  Prolonged action potential and decreased outward K(+) currents are consistent findings in hypertrophic myocardium. The relation between action potential prolongation and myocyte hypertrophy has remained unclear. The present study investigated the temporal relation between action potential prolongation and myocyte hypertrophy, and the effect of enhancing repolarization on myocyte hypertrophy induced by phenylephrine.
  
  
  METHODS
  Neonatal rabbit ventricular myocytes were cultured and treated with 10 μmol/l phenylephrine. At 6 and 48 h after phenylephrine stimulation, myocyte hypertrophic parameters (including myocyte volume, total protein content, and membrane capacitance), action potential duration (APD), and calcineurin activity were measured; meanwhile, the effect of human-ether-a-go-go-related gene (HERG; encoding the αsubunit of rapidly activating delayed rectifier potassium channel) transfection on the above parameters at 48 h of phenylephrine stimulation was also measured.
  
  
  RESULTS
  At 6 h after phenylephrine treatment, APD at 90% repolarization of neonatal rabbit ventricular myocytes was prolonged by 14.3% (P<.05), but myocyte hypertrophy was not found. At 48 h after phenylephrine stimulation, APD at 90% repolarization of neonatal rabbit ventricular myocytes was furthermore prolonged by 18.8% (P<.05); at the same time, myocyte volume, total protein content, membrane capacitance, and calcineurin activity were increased by 40.0%, 41.8%, 36.4%, and 124.1%, respectively (P<.01). Neonatal rabbit ventricular myocytes transfected by pcDNA3-HERG overexpressed I(HERG,tail) current, which was about fourfold higher than I(Kr) (rapidly activating delayed rectifier K(+) current) of neonatal rabbit ventricular myocytes without transfection of HERG. HERG overexpression could accelerate repolarization and shorten APD at 90% repolarization prolonged by phenylephrine and partially inhibit myocyte hypertrophy and calcineurin activation.
  
  
  CONCLUSIONS
  During the myocyte hypertrophy induced by phenylephrine, prolongation of APD at 90% repolarization is not secondary to but precedes myocyte hypertrophy. HERG overexpression could enhance the repolarization and inhibit the calcineurin activation and myocyte hypertrophy induced by phenylephrine.
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, PR China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.forename: Changcong
authors.initials: C
authors.lastname: Cui
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D019703:Calcineurin / Q000378:metabolism; D002316:Cardiotonic Agents / Q000633:toxicity*; D002478:Cells, Cultured; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055786:Gene Knockout Techniques; D020868:Gene Silencing; D005822:Genetic Vectors; D006329:Heart Conduction System / Q000187:drug effects / Q000469:parasitology / Q000503:physiopathology; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D006984:Hypertrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000633:toxicity*; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D014162:Transfection
chemical_list: D002316:Cardiotonic Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D010656:Phenylephrine; D019703:Calcineurin; D011188:Potassium