Distribution of pacemaker function through the tunica muscularis of the canine gastric antrum

1. Interstitial cells of Cajal (ICC) have been shown to generate pacemaker activity in gastrointestinal (GI) muscles. Experiments were performed to ch aracterize the TCC, within the canine gastric antrum and to determine the s ite(s) of pacemaker activity and whether active propagation pathways exist within the thick-walled tunica muscularis of large mammals. 2. Immunohistochemistry and electron microscopy revealed four populations o f ICC within the antral muscularis on the basis of anatomical location. Typ ical ICC were found in the myenteric region of the small intestine (IC-MY). Intramuscular ICC (TC-IM) were intermingled between muscle fibres of circu lar and longitudinal muscle lavers. ICC were also found within septa (IC-SE P) between muscle bundles and along the submucosal surface of the circular muscle layer (IC-SM). ICC were identified in each location by ultrastructur al features. 3. Intracellular electrical recordings demonstrated nifedipine-insensitive slow waves throughout the circular muscle laver. Separation of interior and submucosal circular muscle strips from the dominant (myenteric) pacemaker region dramatically slowed frequency but did not block spontaneous slow wav es, suggesting that pacemaker cells populate all regions of the circular mu scle. 4. Slow waves could be evoked in interior and submucosal circular muscles a t rates above normal antral frequency by electrical pacing or by acetylchol ine (0.3 muM). Active slow wave propagation occurred in all regions of the circular muscle, and propagation velocities were similar in each region. 5. In summary, antral muscles of the canine stomach have pacemaker capabili ty throughout the circular muscle. Normally, a dominant pacemaker near the myenteric plexus drives slow waves that actively propagate throughout the c ircular laver. Pacemaker activity and the active propagation pathway may oc cur in networks of ICC that are distributed in the region of the myenteric plexus and throughout the circular muscle laver.