Keef Kathleen D, Cobine Caroline A
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA.
J Neurogastroenterol Motil. 2019 Apr 30;25(2):189-204. doi: 10.5056/jnm18172.
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 channels and electromechanical coupling (ie, summation of asynchronous phasic activity, partial tetanus, and window current), whereas the fourth involves the regulation of myofilament Ca 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.
肛管内括约肌（IAS）在维持大便失禁方面起着重要作用，因为它能产生张力，且负责超过70%的静息肛管压力。在正常排便过程中，IAS会放松。从历史上看，胃肠道肌肉的张力产生归因于平滑肌细胞直接产生的机制，即肌源性活动。然而，现在已知慢波在调节胃肠动力中起基本作用，并且这些电活动是由 Cajal 间质细胞产生的。最近，在IAS中也发现了 Cajal 间质细胞以及慢波，这使得它们成为产生张力的可能候选者。在这篇综述中，我们讨论了四种可能导致IAS产生张力的不同机制。其中三种涉及膜电位、L型钙通道和机电耦合（即异步相性活动的总和、部分强直收缩和窗电流），而第四种涉及肌丝钙敏感性的调节。IAS中的收缩活动也受到交感运动神经元的调节，交感运动神经元会显著增加张力和肛管压力，以及抑制性运动神经元（特别是含氮能和血管活性肠肽能的神经元），这些抑制性运动神经元会消除收缩并协助正常排便。IAS运动的改变与诸如大便失禁和肛裂等疾病相关，这些疾病会显著降低生活质量。更详细地了解IAS中张力是如何调节的，对于开发针对这些使人衰弱的排便障碍的更有效治疗策略很重要。
