[Networks of pacemaker cells for gastrointestinal motility]

In the wall of the digestive tract, there are pacemaker and conduction systems which can be compared with those in the heart. The introduction of c-Kit as a specific marker of the cells, ICCs, have dramatically clarified morphological and functional understanding of the cells. Mutant animals that lack c-Kit lose or decrease intestinal motility. Four classes of ICCs have been identified and these are distributed along the digestive tract in an organ- and tissue-specific manner: 1) IC-MY locate along the myenteric plexus; 2) IC-DMP, along the deep muscular plexus of small intestine; 3) IC-SMP, along the interface between the submucosa and circular muscle layer of large intestine; and 4) IC-IM, within the muscular layer of the stomach and large intestine. Basically, IC-MY and IC-SMP have pacemaker functions, whereas IC-DMP and IC-IM link signals between the enteric nervous system and smooth muscle cells (SMC). All classes of the cells are connected by gap junctions. Immunocytochemical observations using specific antibodies against various gap junction proteins, connexins (Cx), revealed that Cx43 was localized in the gap junctions between SMC and ICCs, whereas Cx45 was specifically expressed in IC-DMP as it is in the cardiac conduction systems. Mutant animals that we produced enabled us to show cells expressing Cx45 mRNA by replacing the Cx45 locus with a LacZ reporter gene and revealed that most of SMC express Cx45, where so far gap junctions were not demonstrated by electron microscopy or immunocytochemistry, probably due to their small size.