Altered expression of a two-pore domain (K2P) mechano-gated potassium channel TREK-1 in Hirschsprung's disease.

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.

Citation

Christian Tomuschat, Anne Marie O'Donnell, David Coyle, Nickolas Dreher, Danielle Kelly, Prem Puri. Altered expression of a two-pore domain (K2P) mechano-gated potassium channel TREK-1 in Hirschsprung's disease. Pediatric research. 2016 Nov;80(5):729-733

Mesh Tags

Substances

PMID: 27384506

search → result