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Studies on colonic autonomic rhythmicity and its pacemaker mechanism in pathological model animals

病理模型动物结肠自主节律性及其起搏机制的研究

基本信息

批准号：
14370189
负责人：
TAKAKI Miyako
金额：
$ 6.72万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370189/
关键词：
pacemaker cell interstitial cells of Cajal Ca channel mitochondria sarcoplasmic reticulum ryanodine receptor IP_3 receptor autonomic rhythmicity

项目摘要

To clarify the generation mechanisms for autonomic rhythmicity (pacemaker mechanisms) in pathological gut model, pacemaker mechanisms in the normal gut was elucidated by various approaches. (1)The role of pacemaker cells located in the submucosa of the mouse proximal colon. (Submucosal interstitial cells of Cajal : ICC-SM) were investigated by direct recording of pacemaker potentials ICC-SM cells. The result revealed the pacemaker potentials of ICC-SM do not contribute to the generation of peristaltic movements in the longitudinal and circular muscles. (2)To clarify the role of pacemaker potentials of ICC-SM cells, the simultaneous recordings of longitudinal and circular muscle contractions and pacemaker potentials of ICC-SM cells were made. The results suggest that pacemaker potentials drive antiperistaltic movements in the proximal colon to absorb the water from the intraluminal contents to make feces. The pacemaker potentials of ICC-SM is mainly generated and controlled by intracellular calcium handling mechanisms. (3)The results from the mutant mouse genetically deficient of myenteric ICC suggest that several ICC networks localized in the gut wall function as mutual supplementary mechanisms and that enteric nervous system has a crucial role on the compensatory mechanism for deficiency of either ICC network. (4)From mouse embryonic stem (ES) cells, the embryoid body and then cell clusters of gut (ES-gut) were differentiated spontaneously after 3 weeks. Ca oscillation was expressed in ES-guts, and ICC & gap junctions were well differentiated. Such ES guts generate peristalsis-like movements at the frequency of 14 -15 min^<-1>. All results indicated that ICC has an important role on autonomic movements. Possible changes of ICC in inflammatory bowel disease model should be further explored.

为了阐明病理性肠道模型中自主节律的产生机制（起搏器机制），通过各种方法阐明了正常肠道中的起搏器机制。（1）位于小鼠近端结肠粘膜下层的起搏细胞的作用。（粘膜下Cajal间质细胞：ICC-SM）通过直接记录起搏电位ICC-SM细胞进行研究。结果表明，ICC-SM的起搏电位对纵肌和环肌的蠕动运动没有贡献。(2)To为阐明ICC-SM细胞起搏电位的作用，同时记录了ICC-SM细胞的纵、环肌收缩和起搏电位。结果表明，起搏电位驱动近端结肠的逆蠕动运动，从管腔内容物中吸收水分以制造粪便。ICC-SM的起搏电位主要由细胞内钙处理机制产生和控制。（3）肌间ICC基因缺失突变小鼠的研究结果提示，肠壁存在多个ICC网络，它们相互补充，肠神经系统在其中一个ICC网络缺失时的代偿机制中起重要作用。（4）小鼠胚胎干细胞（ES细胞）3周后自发分化为拟胚体和肠细胞团（ES-gut）。ES-肠细胞内钙离子振荡，ICC和缝隙连接分化良好。这样的ES肠以14 - 15分钟的频率产生类似痉挛的运动<-1>。上述结果表明，ICC在自主运动中起重要作用。ICC在炎症性肠病模型中的可能变化有待进一步探讨。