title: Assembly of the cardiac intercalated disk during pre- and postnatal development of the human heart.
abstract: BACKGROUND
  In cardiac muscle, the intercalated disk (ID) at the longitudinal cell-edges of cardiomyocytes provides as a macromolecular infrastructure that integrates mechanical and electrical coupling within the heart. Pathophysiological disturbance in composition of this complex is well known to trigger cardiac arrhythmias and pump failure. The mechanisms underlying assembly of this important cellular domain in human heart is currently unknown.
  
  
  METHODS
  We collected 18 specimens from individuals that died from non-cardiovascular causes. Age of the specimens ranged from a gestational age of 15 weeks through 11 years postnatal. Immunohistochemical labeling was performed against proteins comprising desmosomes, adherens junctions, the cardiac sodium channel and gap junctions to visualize spatiotemporal alterations in subcellular location of the proteins.
  
  
  RESULTS
  Changes in spatiotemporal localization of the adherens junction proteins (N-cadherin and ZO-1) and desmosomal proteins (plakoglobin, desmoplakin and plakophilin-2) were identical in all subsequent ages studied. After an initial period of diffuse and lateral labelling, all proteins were fully localized in the ID at approximately 1 year after birth. Nav1.5 that composes the cardiac sodium channel and the gap junction protein Cx43 follow a similar pattern but their arrival in the ID is detected at (much) later stages (two years for Nav1.5 and seven years for Cx43, respectively).
  
  
  CONCLUSIONS
  Our data on developmental maturation of the ID in human heart indicate that generation of the mechanical junctions at the ID precedes that of the electrical junctions with a significant difference in time. In addition arrival of the electrical junctions (Nav1.5 and Cx43) is not uniform since sodium channels localize much earlier than gap junction channels.
authors.affiliation: Department of Medical Physiology, Division of Heart&Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Arnold
authors.initials: A
authors.lastname: Vreeker
authors.affiliation: Department of Medical Physiology, Division of Heart&Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Leonie
authors.initials: L
authors.lastname: van Stuijvenberg
authors.affiliation: The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University College of Engineering, Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hund
authors.affiliation: The Dorothy M. Davis Heart and Lung Research Institute, Department of Physiology & Cell Biology Department of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University Medical Center, Columbus, Ohio, United States of America.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mohler
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Peter G J
authors.initials: PG
authors.lastname: Nikkels
authors.affiliation: Department of Medical Physiology, Division of Heart&Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Toon A B
authors.initials: TA
authors.lastname: van Veen
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D018031:Connexin 43 / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism; D005865:Gestational Age; D006321:Heart / Q000196:embryology* / Q000254:growth & development*; D006352:Heart Ventricles / Q000196:embryology* / Q000254:growth & development*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry
chemical_list: D018031:Connexin 43; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels
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