Functional roles of interstitial cells of Cajal in the GI tract of rats

Interstitial cells of Cajal (ICC) are distributed through the gastrointestinal (GI) tract, but the functional role of these cells comes primarily from studies of mice. Whether the functions of ICC are similar in larger animals is largely speculative. We investigated whether the <i>Kit</i> mutation in <i>Ws/Ws</i> rats had consequences on ICC populations in the stomach, small intestine, and colon and whether loss of ICC resulted in functional defects similar to <i>Kit</i> mutations in mice. Immunohistochemical labeling with c-KIT or ANO1 antibodies revealed loss of intramuscular ICC (ICC-IM) and reduced myenteric ICC (ICC-MY) in the stomachs of <i>Ws/Ws</i> mutants. Disruption of ICC-MY networks but not ICC within the deep muscular plexus (ICC-DMP) was observed in the small intestine. ICC in the proximal colon was reduced, but no population was absent. ICC loss in the stomach caused loss of spontaneous transient depolarizations, reduced pacemaker activity, and reduced responses to cholinergic and nitrergic nerve stimulation. Loss of ICC-MY in the small intestine resulted in abnormal pacemaker activity, but neural responses appeared to be normal. In the proximal colon, tonic inhibition due to ongoing nitrergic neural inputs was reduced, spontaneous spike complexes were less rhythmic, and nitrergic neural responses were reduced. Apamin-sensitive inhibitory neural responses were retained throughout the GI tract. In summary, <i>Ws/Ws</i> rats have lesions in ICC and functional deficits similar to, but not identical to, <i>Kit</i> mutant mice. These larger animals with more robust GI muscles may be useful for investigations into the role of ICC in normal and abnormal GI motility.<b>NEW & NOTEWORTHY</b> The physiological roles of interstitial cells of Cajal (ICC) throughout the gastrointestinal (GI) tract have been derived predominantly from studies of mice. We sought to determine whether reduction in ICC in the rat, a commonly used animal for studies of GI motor functions, leads to functional deficits. <i>Ws/Ws</i> rats display reduced ICC leading to a disruption in pacemaker activity and neuroeffector responses. Our results provide additional evidence for the functions of ICC in the GI tract.