title: Contactin-2 expression in the cardiac Purkinje fiber network.
abstract: BACKGROUND
  Purkinje cells (PCs) comprise the most distal component of the cardiac conduction system, and their unique electrophysiological properties and the anatomic complexity of the Purkinje fiber network may account for the prominent role these cells play in the genesis of various arrhythmic syndromes.
  
  
  RESULTS
  Differential transcriptional profiling of murine Purkinje fibers and working ventricular myocytes was performed to identify novel genes expressed in PCs. The most highly enriched transcript in Purkinje fibers encoded Contactin-2 (Cntn2), a cell adhesion molecule critical for neuronal patterning and ion channel clustering. Endogenous expression of Cntn2 in the murine ventricle was restricted to a subendocardial network of myocytes that also express beta-galactosidase in CCS-lacZ transgenic mice and the connexin40 gap junction protein. Both Cntn2-lacZ knockin mice and Cntn2-EGFP BAC transgenic reporter mice confirmed expression of Cntn2 in the Purkinje fiber network, as did immunohistochemical staining of single canine Purkinje fibers. Whole-cell patch-clamp recordings and measurements of Ca(2+) transients in Cntn2-EGFP(+) cells revealed electrophysiological properties indicative of PCs and distinctive from those of cardiac myocytes, including prolonged action potentials and frequent afterdepolarizations.
  
  
  CONCLUSIONS
  Cntn2 is a novel marker of the specialized cardiac conduction system. Endogenous expression of Cntn2 as well as Cntn2-dependent transcriptional reporters provides a new tool through which Purkinje cell biology and pathophysiology can now more readily be deciphered. Expression of a contactin family member within the CCS may provide a mechanistic basis for patterning of the conduction system network and the organization of ion channels within Purkinje cells.
authors.affiliation: Leon H. Charney Division of Cardiology, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: Benedetta A
authors.initials: BA
authors.lastname: Pallante
authors.forename: Steven
authors.initials: S
authors.lastname: Giovannone
authors.forename: Liu
authors.initials: L
authors.lastname: Fang-Yu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Nian
authors.initials: N
authors.lastname: Liu
authors.forename: Guoxin
authors.initials: G
authors.lastname: Kang
authors.forename: Wen
authors.initials: W
authors.lastname: Dun
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Boyden
authors.forename: Glenn I
authors.initials: GI
authors.lastname: Fishman
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism*; D058969:Contactin 2; D004285:Dogs; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000166:cytology; D018408:Patch-Clamp Techniques; D011690:Purkinje Fibers / Q000166:cytology / Q000502:physiology*; D012508:Sarcolemma / Q000502:physiology
chemical_list: D015415:Biomarkers; D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D049452:Green Fluorescent Proteins