J Neurogastroenterol Motil 2019; 25(2): 316-331  
Colonic Transit Disorder Mediated by Downregulation of Interstitial Cells of Cajal/Anoctamin-1 in Dextran Sodium Sulfate-induced Colitis Mice
Chen Lu,1,2 Hongli Lu,1 Xu Huang,1 Shaohua Liu,3 Jingyu Zang,2 Yujia Li,1 Jie Chen,2 and Wenxie Xu1*
1Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Department of Pediatric Surgery, Xin Hua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; and 3Department of Anesthesiology, South Renji Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Correspondence to: *Wenxie Xu, PhD
Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, No. 800, Dongchuan Road, Shanghai 200240, China, Tel: +86-21-34205639, Fax: +86-21-34205639, E-mail: wenxiexu@sjtu.edu.cn
Received: October 30, 2018; Revised: January 15, 2019; Accepted: February 26, 2019; Published online: April 30, 2019.
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims: Interstitial cells of Cajal (ICC) and their special calcium-activated chloride channel, anoctamin-1 (ANO1) play pivotal roles in regulating colonic transit. This study is designed to investigate the role of ICC and the ANO1 channel in colonic transit disorder in dextran sodium sulfate (DSS)-treated colitis mice.
Methods: Colonic transit experiment, colonic migrating motor complexes (CMMCs), smooth muscle spontaneous contractile experiments, intracellular electrical recordings, western blotting analysis, and quantitative polymerase chain reaction were applied in this study.
Results: The mRNA and protein expressions of c-KIT and ANO1 channels were significantly decreased in the colons of DSS-colitis mice. The colonic artificial fecal-pellet transit experiment in vitro was significantly delayed in DSS-colitis mice. The CMMCs and smooth muscle spontaneous contractions were significantly decreased by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), an ANO1 channel blocker, and NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of nitric oxide synthase activity, in DSS-colitis mice compared with that of control mice. Intracellular electrical recordings showed that the amplitude of NPPB-induced hyperpolarization was more positive in DSS-colitis mice. The electric field stimulation-elicited nitric-dependent slow inhibitory junctional potentials were also more positive in DSS-colitis mice than those of control mice.
Conclusion: The results suggest that colonic transit disorder is mediated via downregulation of the nitric oxide/ICC/ANO1 signalling pathway in DSS-colitis mice.
Keywords: Anoctamin-1; Colitis; Interstitial cells of Cajal; Nitric oxide synthase; Down-regulation


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