PACEMAKER CELLS IN THE GASTROINTESTINAL-TRACT - INTERSTITIAL-CELLS OFCAJAL

Interstitial cells of Cajal (ICC) were described a century ago as prim itive neurons in the intestines. Through the years, ICC have been mist aken for neurons, glial cells, fibroblasts, smooth muscle cells, and m acrophages. We identified ICC in the musculature of mouse small intest ine by their characteristic morphology and topography, and we analysed the relation between ICC, autonomic nerves, and smooth muscle. Subseq uent morphological and electrophysiological evidence has strongly supp orted our hypotheses that some ICC populations are gut pacemakers and may hold other fundamental regulatory functions (coordinative, mechano receptive, mediating nervous input). Recognition of common principles of ICC organization (confinement to specific locations in relation to smooth muscle layers; formation of extensive cellular networks through tight coupling of overlapping thin processes; innervation patterns; c haracteristic patterns of contact with smooth muscle cells) and ultras tructure (myoid features: basal lamina, caveolae, rich in sER and mito chondria, often prominent filament bundles and dense bands/bodies) has allowed the identification of ICC in the GI musculature of all specie s investigated. However, variation in organization and ultrastructure is significant, between both species and regions of the GI tract. Our studies of ICC in human intestine permit an extension of the above hyp otheses to man and provide a basis for further studies of ICC patholog y and pathophysiology. The latter may become a fruitful area of resear ch in the coming decades.