The Importance of Interstitial Cells of Cajal in the Gastrointestinal Tract

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Abstract

Gastrointestinal (GI) motility function and its regulation is a complex process involving collaboration and communication of multiple cell types such as enteric neurons, interstitial cells of Cajal (ICC), and smooth muscle cells. Recent advances in GI research made a better understanding of ICC function and their role in the GI tract, and studies based on different types of techniques have shown that ICC, as an integral part of the GI neuromuscular apparatus, transduce inputs from enteric motor neurons, generate intrinsic electrical rhythmicity in phasic smooth muscles, and have a mechanical sensation ability. Absence or improper function of these cells has been linked to some GI tract disorders. This paper provides a general overview of ICC; their discovery, subtypes, function, locations in the GI tract, and some disorders associated with their loss or disease, and highlights some controversial issues with regard to the importance of ICC in the GI tract.

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Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract.

Pedro J Gomez-Pinilla, Simon J Gibbons, Michael Bardsley … (2009)

Populations of interstitial cells of Cajal (ICC) are altered in several gastrointestinal neuromuscular disorders. ICC are identified typically by ultrastructure and expression of Kit (CD117), a protein that is also expressed on mast cells. No other molecular marker currently exists to independently identify ICC. The expression of ANO1 (DOG1, TMEM16A), a Ca(2+)-activated Cl(-) channel, in gastrointestinal stromal tumors suggests it may be useful as an ICC marker. The aims of this study were therefore to determine the distribution of Ano1 immunoreactivity compared with Kit and to establish whether Ano1 is a reliable marker for human and mouse ICC. Expression of Ano1 in human and mouse stomach, small intestine, and colon was investigated by immunofluorescence labeling using antibodies to Ano1 alone and in combination with antibodies to Kit. Colocalization of immunoreactivity was demonstrated by epifluorescence and confocal microscopy. In the muscularis propria, Ano1 immunoreactivity was restricted to cells with the morphology and distribution of ICC. All Ano1-positive cells in the muscularis propria were also Kit positive. Kit-expressing mast cells were not Ano1 positive. Some non-ICC in the mucosa and submucosa of human tissues were Ano1 positive but Kit negative. A few (3.2%) Ano1-positive cells in the human gastric muscularis propria were labeled weakly for Kit. Ano1 labels all classes of ICC and represents a highly specific marker for studying the distribution of ICC in mouse and human tissues with an advantage over Kit since it does not label mast cells.

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Anorectal malformations

Marc Levitt, Alberto Peña-Valenzuela (2007)

Anorectal malformations comprise a wide spectrum of diseases, which can affect boys and girls, and involve the distal anus and rectum as well as the urinary and genital tracts. They occur in approximately 1 in 5000 live births. Defects range from the very minor and easily treated with an excellent functional prognosis, to those that are complex, difficult to manage, are often associated with other anomalies, and have a poor functional prognosis. The surgical approach to repairing these defects changed dramatically in 1980 with the introduction of the posterior sagittal approach, which allowed surgeons to view the anatomy of these defects clearly, to repair them under direct vision, and to learn about the complex anatomic arrangement of the junction of rectum and genitourinary tract. Better imaging techniques, and a better knowledge of the anatomy and physiology of the pelvic structures at birth have refined diagnosis and initial management, and the analysis of large series of patients allows better prediction of associated anomalies and functional prognosis. The main concerns for the surgeon in correcting these anomalies are bowel control, urinary control, and sexual function. With early diagnosis, management of associated anomalies and efficient meticulous surgical repair, patients have the best chance for a good functional outcome. Fecal and urinary incontinence can occur even with an excellent anatomic repair, due mainly to associated problems such as a poorly developed sacrum, deficient nerve supply, and spinal cord anomalies. For these patients, an effective bowel management program, including enema and dietary restrictions has been devised to improve their quality of life.

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Gut peristalsis is governed by a multitude of cooperating mechanisms.

Jan D. Huizinga, Wim Lammers (2008)

Peristaltic motor activity of the gut is an essential activity to sustain life. In each gut organ, a multitude of overlapping mechanisms has developed to acquire the ability of coordinated contractile activity under a variety of circumstances and in response to a variety of stimuli. The presence of several simultaneously operating control systems is a challenge for investigators who focus on the role of one particular control activity since it is often not possible to decipher which control systems are operating or dominant in a particular situation. A crucial advantage of multiple control systems is that gut motility control can withstand injury to one or more of its components. Our efforts to increase understanding of control mechanism are not helped by recent attempts to eliminate proven control systems such as interstitial cells of Cajal (ICC) as pacemaker cells, or intrinsic sensory neurons, nor does it help to view peristalsis as a simple reflex. This review focuses on the role of ICC as slow-wave pacemaker cells and places ICC into the context of other control mechanisms, including control systems intrinsic to smooth muscle cells. It also addresses some areas of controversy related to the origin and propagation of pacemaker activity. The urge to simplify may have its roots in the wish to see the gut as a consequence of a single perfect design experiment whereas in reality the control mechanisms of the gut are the messy result of adaptive changes over millions of years that have created complementary and overlapping control systems. All these systems together reliably perform the task of moving and mixing gut content to provide us with essential nutrients.

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Author and article information

Journal

Journal ID (nlm-ta): Saudi J Gastroenterol

Journal ID (iso-abbrev): Saudi J Gastroenterol

Journal ID (publisher-id): SJG

Title: Saudi Journal of Gastroenterology : Official Journal of the Saudi Gastroenterology Association

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Print): 1319-3767

ISSN (Electronic): 1998-4049

Publication date (Print): Jan-Feb 2013

Volume: 19

Issue: 1

Pages: 3-15

Affiliations

[1]Department of Physiology, Jordan University of Science and Technology, Irbid, Jordan

Author notes

Address for correspondence: Dr. Othman Abdullah Al-Shboul, Department of Physiology, Jordan University of Science and Technology, P.O. Box 3030, Irbid - 22110, Jordan. E-mail: oashboul@ 123456just.edu.jo

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Publisher ID: SJG-19-3

DOI: 10.4103/1319-3767.105909

PMC ID: 3603487

PubMed ID: 23319032

SO-VID: 7bbbdfa2-c375-4edb-af3e-857678db9e0a

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The Importance of Interstitial Cells of Cajal in the Gastrointestinal Tract

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Karger: Gastroenterology

Most cited references 140

Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract.

Anorectal malformations

Gut peristalsis is governed by a multitude of cooperating mechanisms.

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