title: Funny current channel HCN4 delineates the developing cardiac conduction system in chicken heart.
abstract: BACKGROUND
  Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) in the mouse is expressed in the developing cardiac conduction system (CCS). In the sinoatrial node (SAN), HCN4 is the predominant isoform responsible for the funny current. To date, no data are available on HCN4 expression during chicken CCS development.
  
  
  OBJECTIVE
  The purpose of this study was to provide the full-length sequence of Hcn4 and describe its expression pattern during development in relation to the CCS in the chicken embryo.
  
  
  METHODS
  Hcn4 RNA expression was studied by in situ hybridization in sequential chick developmental stages (HH11-HH35) and immunohistochemical staining was conducted for the myocardial protein cardiac troponin I and the cardiac transcription factor Nkx2.5.
  
  
  RESULTS
  We obtained the full-length sequence of Hcn4 in chick. Hcn4 expression was observed early in development in the primary heart tube. At later stages, expression became restricted to transitional zones flanked by working myocardium, comprising the sinus venosus myocardium where the SAN develops, the atrioventricular canal myocardium, the primary fold (a myocardial zone between the developing ventricles), and the developing outflow tract. Further in development, Hcn4 expression was restricted to the SAN, the atrioventricular node, the common bundle, the bundle branches, and the internodal and atrioventricular ring myocardium.
  
  
  CONCLUSIONS
  We have identified Hcn4 as a marker of the developing CCS in the chick. The primary heart tube expresses Hcn4, which is later restricted to the transitional zones and eventually the elements of the mature CCS. Furthermore, we hypothesize that expression patterns during development may delineate potential arrhythmogenic sites in the adult heart.
authors.affiliation: Department of Anatomy & Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Vicente-Steijn
authors.forename: Robert
authors.initials: R
authors.lastname: Passier
authors.forename: Lambertus J
authors.initials: LJ
authors.lastname: Wisse
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schalij
authors.forename: Robert E
authors.initials: RE
authors.lastname: Poelmann
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
authors.forename: Monique R M
authors.initials: MR
authors.lastname: Jongbloed
mesh_terms: D000818:Animals; D002642:Chick Embryo; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D006329:Heart Conduction System / Q000196:embryology* / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012849:Sinoatrial Node / Q000378:metabolism* / Q000502:physiology; D013997:Time Factors
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D012333:RNA, Messenger