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

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• 作者：Christian Tomuschat^a ; Anne Marie O'Donnell^a ; David Coyle^a ; Nickolas Dreher^a ; Danielle Kelly^a ; Prem Puri^a ; ^b ; ^{prem.puri@ncrc.ie" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hirschsprung's Disease ; K(ATP) channels ; Hirschsprung's associated enterocolitis (HAEC) ; Inflammatory bowel disease
• 刊名：Journal of Pediatric Surgery
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：51
• 期：6
• 页码：948-952
• 全文大小：700 K

文摘

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.