Pacemaker Cells in the Gastrointestinal Tract: Interstitial Cells of Cajal

Abstract

Interstitial cells of Cajal (ICC) were described a century ago as primitive neurons in the intestines. Through the years, ICC have been mistaken for neurons, glial cells, fibroblasts, smooth muscle cells, and macrophages. We identified ICC in the musculature of mouse small intestine by their characteristic morphology and topography, and we analysed the relation between ICC, autonomic nerves, and smooth muscle. Subsequent morphological and electrophysiological evidence has strongly supported our hypotheses that some ICC populations are gut pacemakers and may hold other fundamental regulatory functions (coordinative, mechanoreceptive, 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; characteristic patterns of contact with smooth muscle cells) and ultrastructure (myoid features: basal lamina, caveolae, rich in sER and mitochondria, often prominent filament bundles and dense bands/bodies) has allowed the identification of ICC in the GI musculature of all species 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 hypotheses to man and provide a basis for further studies of ICC pathology and pathophysiology. The latter may become a fruitful area of research in the coming decades.

Key Words:

• Colon
• motility
• small intestine
• smooth muscle
• ultrastructure