The interstitial cells of Cajal and a gastroenteric pacemaker system

In spite of a claim by Kobayashi (1990) that they do not correspond to the cells originally depicted by CAJAL, a particular category of fibroblast-like cells have been identified in the gut by electron microscopy (Faussone-Pellegrini, 1977; Thuneberg, 1980) and by immunohistochemistry for Kit protein (Maeda et al., 1992) under the term of the "interstitial cells of Cajal (ICC)". Generating electrical slow waves, the ICC are intercalated between the intramural neurons and the effector smooth muscular cells, to form a gastroenteric pacemaker system. ICC at the level of the myenteric plexus (IC-MY) are multipolar cells forming a reticular network. The network of IC-MY which is believed to be the origin of electrical slow waves is morphologically independent from but associated with the myenteric plexus. On the other hand, intramuscular ICC (IC-IM) usually have spindle-shaped contours arranged in parallel with the bulk smooth muscle cells. Associated with nerve bundles and blood vessels, the IC-IM possess receptors for neurotransmitters and such circulating hormones as cholecystokinin, suggesting their roles in neuromuscular and hormone-muscular transmissions. In addition, gap junctions connect the IC-MY and IC-IM, thereby realizing the electrically synchronized integrity of ICC as a pacemaker system in the gut. The smooth muscle cells are also coupled with ICC via gap junctions, and the functional unit thus formed enables rhythmically synchronized contractions and relaxations. It has recently been found that a lack of Kit-expressing cells may induce hyper-contractility of the tunica muscularis in vitro, whereas a decrease in Kit expression within the muscle wall causes dysmotility-like symptoms in vivo. The pacemaker system in the gut thus seems to play a critical role in the maintenance of both moderate and normal motility of the digestive tract. A loss of Kit positive cells has been detected in several diseases with an impaired motor activity, including diabetic gastroenteropathy. Pathogenesis of these diseases is thought to be accounted for by impaired slow waves and neuromuscular transmissions; a pacemaker disorder may possibly induce a dysmotility-like symptom called 'gastroenteric arrhythmia'. A knowledge of the structure and function of the ICC and the pacemaker system provides a basis for clarifying the normal mechanism and the pathophysiology of motility in the digestive tract.