title: Altered expression of a two-pore domain (K2P) mechano-gated potassium channel TREK-1 in Hirschsprung's disease.
abstract: The pathophysiology of Hirschsprung's disease (HSCR) is not fully understood. A significant proportion of patients have persisting bowel symptoms such as constipation, soiling, and enterocolitis despite correctly performed operations. Animal data suggest that stretch-activated 2-pore domain K+channels play a critical role in the maintenance of intestinal barrier integrity.
  
  
  
  We investigated TREK-1 protein expression in ganglionic and aganglionic regions of HSCR patients (n = 10) vs. normal control colon (n = 10). Protein distribution was assessed by using immunofluorescence and confocal microscopy. Gene and protein expression were quantified using quantitative real-time polymerase chain reaction, western blot analysis, and densitometry.
  
  
  
  Confocal microscopy of the normal colon revealed strong TREK-1 channel expression in the epithelium. TREK-1-positive cells were decreased in aganglionic and ganglionic bowel compared to controls. TREK-1 gene expression levels were significantly decreased in aganglionic and ganglionic bowel compared to controls (P < 0.05). Western blotting revealed decreased TREK-1 protein expression in aganglionic and ganglionic bowel compared to controls.
  
  
  
  We demonstrate, for the first time, the expression and distribution of TREK-1 channels in the human colon. The decreased TREK-1 expression in the aganglionic and ganglionic bowel observed in HSCR may alter intestinal epithelial barrier function leading to the development of enterocolitis.
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.
authors.forename: Christian
authors.initials: C
authors.lastname: Tomuschat
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, 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, Dublin, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Coyle
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.
authors.forename: Nickolas
authors.initials: N
authors.lastname: Dreher
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.
authors.forename: Danielle
authors.initials: D
authors.lastname: Kelly
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.|School of Medicine and Medical Science and Conway Institute of Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
mesh_terms: D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006627:Hirschsprung Disease / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D008297:Male; D018613:Microscopy, Confocal; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D000072417:Protein Domains
chemical_list: D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1