title: Decreased expression of Kv7 channels in Hirchsprung's disease.
abstract: OBJECTIVE
  Voltage-dependent K+channels (Kv channels) participate in electrical rhythmicity and smooth muscle responses and are regulated by excitatory and inhibitory neurotransmitters. Kv channels also participate in the interstitial cell of Cajal (ICC) and smooth muscle cell (SMC) responses to neural inputs. The Kv family consists of 12 subfamilies, Kv1-Kv12, with five members of the Kv7 family identified to date: Kv7.1-Kv7.5. A recent study identified the potassium channel Kv7.5 as having a role in the excitability of ICC-IM in the mouse colon. We therefore designed this study to test the hypothesis that Kv7 channels are present in the normal human colon and are reduced in Hirschprung's disease (HSCR).
  
  
  METHODS
  HSCR tissue specimens were collected at the time of pull-through surgery (n=10), while normal control tissue specimens were obtained at the time of colostomy closure in patients with imperforate anus (n=10). Kv7.3-Kv7.5 immunohistochemistry was performed and visualized using confocal microscopy to assess their distribution. Western blot analysis was undertaken to determine Kv7.3-Kv7.5 protein quantification.
  
  
  RESULTS
  Kv7.3 and Kv7.4-immunoreactivity was co-localized with neuron and ICC markers, while Kv7.5 was found to be expressed on both ICCs and SMCs. Western blot analysis revealed similar levels of Kv7.3 and Kv7.5 expression in the normal colon and HSCR colon, while Kv7.4 proteins were found to be markedly decreased in ganglionic specimens and decreased further in aganglionic specimens.
  
  
  CONCLUSIONS
  A deficiency of Kv7.4 channels in the ganglionic and aganglionic bowel may place a role in colonic dysmotility in HSCR.
authors.affiliation: National Children's Research Center, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: O'Donnell
authors.affiliation: National Children's Research Center, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Coyle
authors.affiliation: National Children's Research Center, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland; School of Medicine and Medical Science and Conway Institute of Biomedical Research, University College Dublin, Ireland. Electronic address: prem.puri@ncrc.ie.
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D003106:Colon / Q000601:surgery; D005455:Fluorescent Antibody Technique; D006627:Hirschsprung Disease / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D056885:Interstitial Cells of Cajal / Q000378:metabolism*; D009130:Muscle, Smooth / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018377:Neurotransmitter Agents; D015221:Potassium Channels
keywords: Enteric nervous system; Hirschsprung's disease; Interstitial cells of Cajal; Voltage-dependent potassium channels