Control of Motility in the Internal Anal Sphincter

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 Ca 2+ channels and electromechanical coupling (ie, summation of asynchronous phasic activity, partial tetanus, and window current), whereas the fourth involves the regulation of myofilament Ca 2+ 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.

Rhythmic calcium transients in smooth muscle cells of the mouse internal anal sphincter

“…We have hypothesized that phasic Ca 2+ entry events give rise to tone . One mechanism that may be involved relates to SW frequency.…”

“…We have hypothesized that phasic Ca 2+ entry events give rise to tone. 13,14 One mechanism that may be involved relates to SW frequency. The frequency of SWs in the IAS is significantly greater than that of other gastrointestinal (GI) muscles that do not generate tone (eg, 30 cpm vs 8 cpm for the dog IAS vs rectum 9 ).…”

“…Contraction and SWs in the IAS are dependent upon Ca 2+ entry through Cav L because both are abolished by Cav L blockers or by hyperpolarizing membrane potential below the Cav L activation threshold with the K ATP channel activator pinacidil 9,[12][13][14]. AdditionalF I G U R E 3 Examples of the origin and spread of Ca 2+ transients.…”

“…Distance is plotted on the x-axis (proximal edge on left) and time on the y-axis (zero time at top). B, Comparison of CTs recorded at the distal extremity of the IAS (upper black trace) IAS including Cav L -dependent (eg, partial tetanus, window current, asynchronous muscle bundle summation) and Cav L -independent ones (eg, myofilament sensitivity) 14. The relevance of each…”

HYPHYCA: a prospective study in 613 patients conducting a comprehensive analysis for predictive factors of physiological 18F-FDG anal uptake

“…The arrival of materials in the rectal ampoule physiologically leads to an associative sampling reflex associating a propulsive rectal contraction, a relaxation of the internal anal sphincter and a reflex contraction of the external anal sphincter. The subsequent stage, continence or defecation, is under the control of the will of the individual who chooses to respond or not to the exonerating need [17]. Therefore, we can hypothesize that the anal canal uptake could be linked to the voluntary solicitation of the external anal sphincter at the time of the FDG injection and/or during the uptake FDG period.…”