Clinical Trials Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2015; 21(18): 5635-5640
Published online May 14, 2015. doi: 10.3748/wjg.v21.i18.5635
Decreased expression of hyperpolarisation-activated cyclic nucleotide-gated channel 3 in Hirschsprung’s disease
Anne Marie O’Donnell, David Coyle, Prem Puri
Anne Marie O’Donnell, David Coyle, Prem Puri, National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland
Author contributions: O’Donnell AM and Puri P contributed to study conception; O’Donnell AM and Coyle D performed the experiments; all authors contributed to drafting the manuscript; O’Donnell AM and Puri P drafted the final manuscript.
Supported by National Children’s Research Centre/Children’s Medical Research Foundation, Ireland.
Ethics approval: The study was reviewed and approved by the Temple Street Children’s University Hospital Research Ethics Committee No. 13.003.
Clinical trial registration: No clinical trial registration information is available for this study.
Informed consent: Informed written consent for participation in the study was provided by all parents and legal guardians of participants prior to enrollment in the study.
Conflict-of-interest: The authors declare that they have no conflict of interest.
Data sharing: Dataset is available from the corresponding author at prem.puri@ncrc.ie.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Prem Puri, Professor, MS, FRCS, FRCS (Ed), FACS, FAAP (Hon.), DSc (Hon.), National Children’s Research Centre, Our Lady’s Children’s Hospital, Cooley Rd, Crumlin, Dublin 12, Ireland. prem.puri@ucd.ie
Telephone: +353-1-4096420 Fax: +353-1-4550201
Received: October 9, 2014
Peer-review started: October 9, 2014
First decision: November 14, 2014
Revised: November 28, 2014
Accepted: December 19, 2014
Article in press: December 22, 2014
Published online: May 14, 2015
Processing time: 221 Days and 16.8 Hours
Core Tip

Core tip: Children with Hirschsprung’s disease experience symptoms of intestinal obstruction due to a spastically contracted aganglionic segment of distal bowel, however the mechanism for this spasticity is incompletely understood. Hyperpolarisation-activated nucleotide-gated channels play a key role in regulating cell excitability in both pacemaker and non-pacing cells. We examined expression of hyperpolarisation-activated nucleotide-gated (HCN) 1-4 in both Hirschsprung’s disease (HSCR) colon and healthy controls. While HCN-1 expression was absent, and HCN-2 and HCN-4 were expressed at similar levels in diseased and healthy bowel, we found HCN-3 to be reduced in aganglionic bowel in HSCR. We suggest deficient HCN3 channels may be involved in the pathophysiology of HSCR.