J Neurogastroenterol Motil 2019; 25(2): 189-204  
Control of Motility in the Internal Anal Sphincter
Kathleen D Keef* and Caroline A Cobine
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA
Correspondence to: *Kathleen D Keef, PhD
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA, Tel: +1-775-784-4302, Fax: +1-775-784-6903, E-mail: kkeef@med.unr.edu
Received: October 25, 2018; Revised: November 28, 2018; Accepted: December 9, 2018; 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
The internal anal sphincter (IAS) plays an important role in the maintenance of fecal continence since it generates tone and is responsible for > 70% of resting anal pressure. During normal defecation the IAS relaxes. Historically, tone generation in gastrointestinal muscles was attributed to mechanisms arising directly from smooth muscle cells, ie, myogenic activity. However, slow waves are now known to play a fundamental role in regulating gastrointestinal motility and these electrical events are generated by the interstitial cells of Cajal. Recently, interstitial cells of Cajal, as well as slow waves, have also been identified in the IAS making them viable candidates for tone generation. In this review we discuss four different mechanisms that likely contribute to tone generation in the IAS. Three of these involve membrane potential, L-type Ca2+ channels and electromechanical coupling (ie, summation of asynchronous phasic activity, partial tetanus, and window current), whereas the fourth involves the regulation of myofilament Ca2+ sensitivity. Contractile activity in the IAS is also modulated by sympathetic motor neurons that significantly increase tone and anal pressure, as well as inhibitory motor neurons (particularly nitrergic and vasoactive intestinal peptidergic) that abolish contraction and assist with normal defecation. Alterations in IAS motility are associated with disorders such as fecal incontinence and anal fissures that significantly decrease the quality of life. Understanding in greater detail how tone is regulated in the IAS is important for developing more effective treatment strategies for these debilitating defecation disorders.
Keywords: Interstitial cells of Cajal; Receptor, platelet-derived growth factor alpha; Slow waves; Smooth muscle; Tone


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