A CASE FOR INTERSTITIAL-CELLS OF CAJAL AS PACEMAKERS AND MEDIATORS OFNEUROTRANSMISSION IN THE GASTROINTESTINAL-TRACT

Electrical rhythmicity in gastrointestinal muscles has been studied fo r a century, but the pacemakers driving this phenomenon have been elus ive, Anatomic studies suggest that interstitial cells of Cajal (ICC) m ay be pacemakers and conductors of electrical activity. ICC may also m ediate neurotransmission from enteric neurons. Functional evaluations of ICC include the following. (1) Electrophysiology experiments on dis sected muscle strips show that slow waves originate from specific site s, These pacemaker areas are populated by networks of ICC that make ga p junctions with smooth muscle cells, Removal of pacemaker regions int erferes with slow wave generation and propagation. (2) Chemicals that label ICC histochemically can damage ICC and abolish rhythmicity, (3) Isolated ICC are spontaneously active, and several voltage-dependent i on channels, including a low-threshold Ca2+ conductance, ave expressed . (4) ICC are innervated by enteric neurons, and they respond to neuro transmitters. ICC may produce nitric oxide and amplify inhibitory neur otransmission. (5) Some classes of ICC fail to develop in animals with mutations in c-kit or stem cell factor, the ligand for c-Kit receptor s. Without ICC, electrical slow waves are absent. Many questions remai n about the function of ICC, but modern technologies should now facili tate vapid progress toward determining the role of these cells in norm al physiology and pathological conditions.