title: Connexin43 contributes to electrotonic conduction across scar tissue in the intact heart.
abstract: Studies have demonstrated non-myocytes, including fibroblasts, can electrically couple to myocytes in culture. However, evidence demonstrating current can passively spread across scar tissue in the intact heart remains elusive. We hypothesize electrotonic conduction occurs across non-myocyte gaps in the heart and is partly mediated by Connexin43 (Cx43). We investigated whether non-myocytes in ventricular scar tissue are electrically connected to surrounding myocardial tissue in wild type and fibroblast-specific protein-1 driven conditional Cx43 knock-out mice (Cx43fsp1KO). Electrical coupling between the scar and uninjured myocardium was demonstrated by injecting current into the myocardium and recording depolarization in the scar through optical mapping. Coupling was significantly reduced in Cx43fsp1KO hearts. Voltage signals were recorded using microelectrodes from control scars but no signals were obtained from Cx43fsp1KO hearts. Recordings showed significantly decreased amplitude, depolarized resting membrane potential, increased duration and reduced upstroke velocity compared to surrounding myocytes, suggesting that the non-excitable cells in the scar closely follow myocyte action potentials. These results were further validated by mathematical simulations. Optical mapping demonstrated that current delivered within the scar could induce activation of the surrounding myocardium. These data demonstrate non-myocytes in the scar are electrically coupled to myocytes, and coupling depends on Cx43 expression.
authors.affiliation: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY,10016, USA.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Mahoney
authors.affiliation: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY,10016, USA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Mezzano
authors.affiliation: Computational Biology, Department of Computer Science, University of Oxford, Oxford, United Kingdom.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Mirams
authors.affiliation: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY,10016, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Maass
authors.affiliation: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY,10016, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY,10016, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Cerrone
authors.affiliation: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY,10016, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Vasquez
authors.affiliation: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY,10016, USA.
authors.forename: Aneesh
authors.initials: A
authors.lastname: Bapat
authors.affiliation: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY,10016, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Delmar
authors.affiliation: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY,10016, USA.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Morley
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017097:Electric Impedance; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology
chemical_list: D018031:Connexin 43