Hwang Sung Jin, Kwon Joong Goo, Beckett Elizabeth A H, Kim Minkyung, Herbert Tom, Sanders Kenton M, Ward Sean M
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States.
Am J Physiol Gastrointest Liver Physiol. 2025 Jun 1;328(6):G677-G695. doi: 10.1152/ajpgi.00036.2025. Epub 2025 Apr 15.
Interstitial cells of Cajal (ICC) are distributed through the gastrointestinal (GI) tract, but the functional role of these cells comes primarily from studies of mice. Whether the functions of ICC are similar in larger animals is largely speculative. We investigated whether the mutation in rats had consequences on ICC populations in the stomach, small intestine, and colon and whether loss of ICC resulted in functional defects similar to mutations in mice. Immunohistochemical labeling with c-KIT or ANO1 antibodies revealed loss of intramuscular ICC (ICC-IM) and reduced myenteric ICC (ICC-MY) in the stomachs of mutants. Disruption of ICC-MY networks but not ICC within the deep muscular plexus (ICC-DMP) was observed in the small intestine. ICC in the proximal colon was reduced, but no population was absent. ICC loss in the stomach caused loss of spontaneous transient depolarizations, reduced pacemaker activity, and reduced responses to cholinergic and nitrergic nerve stimulation. Loss of ICC-MY in the small intestine resulted in abnormal pacemaker activity, but neural responses appeared to be normal. In the proximal colon, tonic inhibition due to ongoing nitrergic neural inputs was reduced, spontaneous spike complexes were less rhythmic, and nitrergic neural responses were reduced. Apamin-sensitive inhibitory neural responses were retained throughout the GI tract. In summary, rats have lesions in ICC and functional deficits similar to, but not identical to, mutant mice. These larger animals with more robust GI muscles may be useful for investigations into the role of ICC in normal and abnormal GI motility. The physiological roles of interstitial cells of Cajal (ICC) throughout the gastrointestinal (GI) tract have been derived predominantly from studies of mice. We sought to determine whether reduction in ICC in the rat, a commonly used animal for studies of GI motor functions, leads to functional deficits. rats display reduced ICC leading to a disruption in pacemaker activity and neuroeffector responses. Our results provide additional evidence for the functions of ICC in the GI tract.
Cajal间质细胞（ICC）分布于胃肠道，但这些细胞的功能主要来自对小鼠的研究。在大型动物中，ICC的功能是否相似很大程度上只是推测。我们研究了大鼠中的突变是否会对胃、小肠和结肠中的ICC群体产生影响，以及ICC的缺失是否会导致与小鼠突变类似的功能缺陷。用c-KIT或ANO1抗体进行免疫组织化学标记显示，突变体大鼠胃中的肌内ICC（ICC-IM）缺失，肌间ICC（ICC-MY）减少。在小肠中观察到ICC-MY网络中断，但深部肌丛内的ICC（ICC-DMP）未受影响。近端结肠中的ICC减少，但没有完全缺失。胃中ICC的缺失导致自发瞬时去极化丧失、起搏活动减少以及对胆碱能和氮能神经刺激的反应减弱。小肠中ICC-MY的缺失导致起搏活动异常，但神经反应似乎正常。在近端结肠中，由于持续的氮能神经输入引起的紧张性抑制减弱，自发尖峰复合波的节律性降低，氮能神经反应减少。整个胃肠道中对蜂毒明肽敏感的抑制性神经反应得以保留。总之，大鼠在ICC方面存在损伤，且功能缺陷与突变小鼠相似但不完全相同。这些具有更强健胃肠道肌肉的大型动物可能有助于研究ICC在正常和异常胃肠运动中的作用。 Cajal间质细胞（ICC）在整个胃肠道中的生理作用主要来自对小鼠的研究。我们试图确定，在常用于胃肠运动功能研究的大鼠中，ICC减少是否会导致功能缺陷。大鼠显示出ICC减少，导致起搏活动和神经效应反应中断。我们的结果为ICC在胃肠道中的功能提供了更多证据。
