Histogenesis, structure and relationships of interstitial cells of Cajal (ICC): from morphology to functional interpretation.

Interstitial cells of Cajal (ICC) have been found exclusively in gut muscle coat, occupying an interstitial position between nerve endings (NE) and smooth muscle cells (SMC). Light microscope stainings of ICC are aspecific and useful only for evidentiating cell body and ramifications strictly intermingled with SMC and nerve fibers. Transmission electron microscope investigation, on the contrary, permits unequivocable identification and detailed description of ICC cytology. The ultrastructural findings have led to consider ICC as a new cell type, with a specific cytology, highly smooth muscle-like. Specialized ICC relationships with surrounding cells have been found, suggesting the existence of an anatomical unit made up of three closely interconnected elements: the NE-ICC-SMC units. The time of this unit appearance and the steps of its cell types cytodifferentiation from foetal to adult life differ according each gut level. A region-specific ICC distribution inside the gut muscle coat and peculiar organizations of ICC surrounding connective tissue have been observed. On these morphological bases an ICC pacemaking role has been suggested. Recordings of spontaneously generated slow waves from some ICC seemed to confirm this role. According to this hypothesis, smooth muscle contraction should be dependent on ICC function and smooth muscle relaxation on inhibitory nerves release. Further morpho-functional investigations and correlations of obtained data are still necessary in order to better clarify the ICC role and its influence or dependence on both nerve and muscle tissues inside each gut level. The identification of the neurotransmitters contained in the NE contacting ICC and/or SMC needs to be pursued.