Gap junctions in intestinal smooth muscle and interstitial cells of Cajal

This manuscript reviews gap junctions' roles in control of intestinal motility. Gap junctions (GJs) of small intestine (SmIn) are found between circular muscle (CM) cells, between interstitial cells of Cajal (ICC) of deep muscular plexus (DMP) and between them and adjacent outer circular muscle (OCM). GJs between longitudinal muscle (LM) cells or between cells of inner circular muscle (ICM) have not been reported. Occasional GJs have been reported between ICC of the myenteric plexus (MyP) and rarely between these ICC and adjacent LM or CM cells, or between ICC within CM and smooth muscle cells. In the colon (Co) of several species a special network of ICC lines the inner border of CM, the submuscular plexus (SP). GJs are found between ICCs and between them and CM cells. The ICC of MyP of Co are associated with LM and CM; occasional GJs exist between ICC and each muscle layer. Small GJs are missed by electron microscopy or light microscopic Immunocytochemistry. Therefore, GJ coupling may exist without demonstrated GJs. The consequences for the pacemaking functions of ICC networks of varied densities of GJ between ICC and between ICC of MyP or DMP or of SP and CM are considered. Connexins (Cxs) that compose intestinal GJs may affect coupling, but are incompletely known. Understanding of the role of GJs in coordinating intestinal motility requires knowing: (1) what passes through gap junctions to couple ICC to smooth muscle cells; (2) what Cx with what conductances and what modulatory controls connect ICC and smooth muscle cells; (3) whether smooth muscles can generate slow waves independent of ICC networks; and (4) what happens to motility, slow waves, and IJPs when GJs are selectively uncoupled.