Interstitial cells of Cajal - their role in pacing and signal transmissionin the digestive system

Interstitial cells of Cajal (ICC) are located in most parts of the digestiv e system. Although they were discovered over 100 years ago, their function began to be unravelled only recently. Morphological observations have led t o a number of hypotheses on the possible physiological roles of ICC: (1) th ese cells may be the source of slow electrical waves recorded in gastrointe stinal (GI) muscles; (2) they participate in the conduction of electrical c urrents, and (3) mediate neural signals between enteric nerves and muscles. These hypotheses were supported by experiments in which the ICC-containing layer was removed surgically, or when ICC were ablated chemically, and as a consequence the slow waves were absent. Electrophysiological experiments on isolated cells confirmed that ICC can generate rhythmic electrical activ ity and can also respond to messenger molecules known to be released from e nteric nerves. In mice mutants deficient in ICC, or in mice treated with an tibody against the protein c-Kit, slow wave activity was impaired. These re sults support the role of ICC as pacemaker cells. Physiological studies hav e shown that ICC in certain GI regions are important for signal transmissio n between nerves and smooth muscle. There is evidence that pathological cha nges in ICC may be associated with GI motility disorders. The full interpre tation of the role of ICC in disease conditions will require much further s tudy on the physiology and pharmacology of these cells.