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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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: Christian Tomuschat, Anne Marie O'Donnell, David Coyle, Nickolas Dreher, Danielle Kelly, Prem Puri
• Journal: Pediatric research (Pediatr Res) Vol. 80 Issue 5 Pg. 729-733 (11 2016) ISSN: 1530-0447 [Electronic] United States
• PMID: 27384506 (Publication Type: Journal Article)

Chemical References

• Potassium Channels, Tandem Pore Domain
• potassium channel protein TREK-1

Topics

• Case-Control Studies
• Colon (metabolism)
• Female
• Gene Expression Regulation
• Hirschsprung Disease (metabolism, physiopathology)
• Humans
• Infant
• Male
• Microscopy, Confocal
• Potassium Channels, Tandem Pore Domain (metabolism)
• Protein Domains