Recent advances in studies of spontaneous activity in smooth muscle: ubiquitous pacemaker cells

The general and specific properties of pacemaker cells, including Kit-negative cells, that are distributed in gastrointestinal, urethral and uterine smooth muscle tissues, are discussed herein. In intestinal tissues, interstitial cells of Cajal (ICC) are heterogeneous in both their forms and roles. ICC distributed in the myenteric layer (ICC-MY) act as primary pacemaker cells for intestinal mechanical and electrical activity. ICC distributed in muscle bundles play a role as mediators of signals from autonomic nerves to smooth muscle cells. A group of ICC also appears to act as a stretch sensor. Intracellular Ca2+ dynamics play a crucial role in ICC-MY pacemaking; intracellular Ca2+ ([Ca2+](i)) oscillations periodically activate plasmalemmal Ca2+-activated ion channels, such as Ca2+-activated Cl(-) channels and/or non-selective cation channels, although the relative contributions of these channels are not defined. With respect to gut motility, both the ICC network and enteric nervous system, including excitatory and inhibitory enteric neurons, play an essential role in producing highly coordinated peristalsis.