title: Enhanced fibroblast-myocyte interactions in response to cardiac injury.
abstract: BACKGROUND
  A critical event in the development of cardiac fibrosis is the transformation of fibroblasts into myofibroblasts. The electrophysiological consequences of this phenotypic switch remain largely unknown.
  
  
  OBJECTIVE
  Determine whether fibroblast activation following cardiac injury results in a distinct electrophysiological phenotype that enhances fibroblast-myocyte interactions.
  
  
  RESULTS
  Neonatal rat myocyte monolayers were treated with media (CM) conditioned by fibroblasts isolated from normal (Fb) and infarcted (MI-Fb) hearts. Fb and MI-Fb were also plated on top of myocyte monolayers at 3 densities. Cultures were optically mapped after CM treatment or fibroblast plating to obtain conduction velocity and action potential duration (APD(70)). Intercellular communication and connexin43 expression levels were assessed. Membrane properties of Fb and MI-Fb were evaluated using patch clamp techniques. MI-Fb CM treatment decreased conduction velocity (11.1%) compared to untreated myocyte cultures. APD(70) was reduced by MI-Fb CM treatment compared to homocellular myocyte culture (9.4%) and Fb CM treatment (6.4%). In heterocellular cultures, MI-Fb conduction velocities were different from Fb at all densities (+29.8%, -23.0%, and -16.7% at 200, 400, and 600 cells/mm(2), respectively). APD(70) was reduced (9.6%) in MI-Fb compared to Fb cultures at 200 cells/mm(2). MI-Fb had more hyperpolarized resting membrane potentials and increased outward current densities. Connexin43 was elevated (134%) in MI-Fb compared to Fb. Intercellular coupling evaluated with gap fluorescence recovery after photobleaching was higher between myocytes and MI-Fb compared to Fb.
  
  
  CONCLUSIONS
  These data demonstrate cardiac injury results in significant electrophysiological changes that enhance fibroblast-myocyte interactions and could contribute to the greater incidence of arrhythmias observed in fibrotic hearts.
authors: Leon H. Charney Division of Cardiology, New York University School of Medicine, Smilow Research Building 8, 810, 522 First Avenue, New York, NY 10016, USA.
authors: Carolina
authors: C
authors: Vasquez
authors: Poornima
authors: P
authors: Mohandas
authors: Karen L
authors: KL
authors: Louie
authors: Najate
authors: N
authors: Benamer
authors: Ashwini C
authors: AC
authors: Bapat
authors: Gregory E
authors: GE
authors: Morley
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D005355:Fibrosis; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018031:Connexin 43; D017077:Culture Media, Conditioned