Interstitial cells of Cajal in enteric neurotransmission.

Specialised cells known as interstitial cells of Cajal (ICCs), distributed in specific locations within the tunica muscularis of the gastrointestinal tract, serve as electrical pacemakers and mediators of enteric neurotransmission. Until recently, evidence to support a functional role of these cells has been, for the most part, indirect. The role of ICCs in pacemaking or neurotransmission has been tested by experiments in which: (i) ICCs were removed by dissection; (ii) ICCs were lesioned by cytotoxic chemicals thought to have specificity for these cells; (iii) the excitability properties and responses to drugs were directly studied in isolated ICCs ; (iv) morphological studies revealed close relationships between ICCs and varicose nerve fibres (see fig 1); and (v) ICCs responded to neurotransmitters when studied using immunohistochemical techniques. 10 Recent findings have shown that several classes of ICCs of the mouse and other species express the receptor tyrosine kinase, Kit. Activation of Kit by its ligand, stem cell factor, or “steel” factor is important in the development of ICCs because blockade of Kit with neutralising antibodies 12 or mutations in c-kit 14 or steel impair the development of ICCs at the level of the myenteric plexus in the small intestine (IC-MY). Loss of IC-MY is associated with abnormal electrical activity in this region of the gut, including loss of electrical slow waves. In the white spotting mutation (W/W),