title: Characterization of gap junction remodeling in epicardial border zone of healing canine infarcts and electrophysiological effects of partial reversal by rotigaptide.
abstract: BACKGROUND
  The border zone of healing myocardial infarcts is an arrhythmogenic substrate, partly the result of structural and functional remodeling of the ventricular gap junction protein, Connexin43 (Cx43). Cx43 in arrhythmogenic substrates is a potential target for antiarrhythmic therapy.
  
  
  RESULTS
  We characterized Cx43 remodeling in the epicardial border zone (EBZ) of healing canine infarcts 5 days after coronary occlusion and examined whether the gap junction-specific agent rotigaptide could reverse it. Cx43 remodeling in the EBZ was characterized by a decrease in Cx43 protein, lateralization, and increased Cx43 phosphorylation at serine (S) 368. Rotigaptide partially reversed the loss of Cx43 but did not affect the increase in S368 phosphorylation, nor did it reverse Cx43 lateralization. Rotigaptide did not prevent conduction slowing in the EBZ, nor did it decrease the induction of sustained ventricular tachycardia by programmed stimulation, although it did decrease the EBZ effective refractory period.
  
  
  CONCLUSIONS
  We conclude that partial reversal of Cx43 remodeling in healing infarct border zone may not be sufficient to restore normal conduction or prevent arrhythmias.
authors.affiliation: Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, NY, USA.
authors.forename: Ester
authors.initials: E
authors.lastname: Macia
authors.forename: Elena
authors.initials: E
authors.lastname: Dolmatova
authors.forename: Candido
authors.initials: C
authors.lastname: Cabo
authors.forename: Alexandra Z
authors.initials: AZ
authors.lastname: Sosinsky
authors.forename: Wen
authors.initials: W
authors.lastname: Dun
authors.forename: James
authors.initials: J
authors.lastname: Coromilas
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Ciaccio
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Boyden
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Wit
authors.forename: Heather S
authors.initials: HS
authors.lastname: Duffy
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D055724:Electrophysiological Phenomena / Q000187:drug effects / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D006329:Heart Conduction System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D009842:Oligopeptides / Q000494:pharmacology*; D010496:Pericardium / Q000378:metabolism* / Q000503:physiopathology; D020127:Recovery of Function / Q000502:physiology*; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*
chemical_list: D009842:Oligopeptides; C477643:rotigaptide