Altered expression of ATP-sensitive K(+) channels in Hirschsprung's disease.

Abstract

PURPOSE:

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.

MAIN 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.

CONCLUSION:

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: Christian Tomuschat, Anne Marie O'Donnell, David Coyle, Nickolas Dreher, Danielle Kelly, Prem Puri
• Journal: Journal of pediatric surgery (J Pediatr Surg) Vol. 51 Issue 6 Pg. 948-52 (Jun 2016) ISSN: 1531-5037 [Electronic] United States
• PMID: 27001456 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Potassium Channels
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (metabolism)
• Blotting, Western
• Colon (metabolism)
• Female
• Fluorescent Antibody Technique
• Ganglia
• Hirschsprung Disease (metabolism)
• Humans
• In Vitro Techniques
• Intestinal Mucosa (metabolism)
• Male
• Potassium Channels (metabolism)