title: Altered expression of ATP-sensitive K(+) channels in Hirschsprung's disease.
abstract: OBJECTIVE
  Hirschsprung's disease-associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in Hirschsprung's disease (HSCR). Altered intestinal epithelial barrier function has been suggested to play a role in the causation of HAEC. In rodent experimental models of colitis, a decreased expression of K(ATP) channels (Subunits: Kir6.1/6.2 and SUR1/2) is reported. We designed this study to determine if K(ATP) channels exist within the human colon and to investigate the expression of different subunits in Hirschsprung's disease.
  
  
  METHODS
  We investigated Kir6.1, Kir6.2, SUR1, and SUR2 expression in ganglionic and aganglionic bowel of HD patients (n=5) and controls (n=5). Western blotting and confocal immunofluorescence were performed.
  
  
  RESULTS
  Western blot analysis revealed that Kir6.1, Kir6.2, SUR1, and SUR2 are strongly expressed in the normal human colon. Kir6.1, Kir6.2, SUR1, and SUR2 expression was significantly decreased in the aganglionic bowel compared to ganglionic bowel and controls. Kir6.1 and SUR1 expression were also significantly decreased in the ganglionic bowel of HSCR patients compared to controls.
  
  
  CONCLUSIONS
  We demonstrate for the first time the existence of K(ATP) channels in the human colon. The decreased K(ATP) channel expression in HSCR specimens suggests that an altered K(ATP) expression may interfere with intestinal epithelium barrier function and predispose to HAEC.
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Christian
authors.initials: C
authors.lastname: Tomuschat
authors.affiliation: National Children's Research Centre, 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 Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Coyle
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Nickolas
authors.initials: N
authors.lastname: Dreher
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Danielle
authors.initials: D
authors.lastname: Kelly
authors.affiliation: National Children's Research Centre, 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: D000255:Adenosine Triphosphate / Q000378:metabolism*; D015153:Blotting, Western; D003106:Colon / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005724:Ganglia; D006627:Hirschsprung Disease / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D015221:Potassium Channels / Q000378:metabolism*
chemical_list: D015221:Potassium Channels; D000255:Adenosine Triphosphate
keywords: Hirschsprung's Disease; Hirschsprung's associated enterocolitis (HAEC); Inflammatory bowel disease; K((ATP)) channels