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

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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.