Loss of interstitial cells of Cajal and development of electrical dysfunction in murine small bowel obstruction

1. Partial obstruction of the murine ileum led to changes in the gross morp hology and ultrastructure of the tunica. muscularis. Populations of interst itial cells of Cajal (ICC) decreased oral, but not aboral, to the site of o bstruction. Since ICC generate and propagate electrical slow waves in gastr ointestinal muscles, we investigated whether the loss of ICC leads to loss of function in partial bowel obstruction. 2. Changes in ICC networks and electrical activity were monitored in the ob structed murine intestine using immunohistochemistry, electron microscopy a nd intracellular electrophysiological techniques. 3. Two weeks following the onset of a partial obstruction, the bowel increa sed in diameter and hypertrophy of the tunica muscularis was observed oral to the obstruction site. ICC networks were disrupted oral to the obstructio n, and this disruption was accompanied by the loss of electrical slow waves and responses to enteric nerve stimulation. These defects were not observe d aboral to the obstruction. 4. Ultrastructural analysis revealed no evidence of cell death in regions w here the lesion in ICC networks was developing. Cells with a morphology int ermediate between Smooth muscle cells and fibroblasts were found in locatio ns that are typically populated by ICC. These cells may have been the redif ferentiated remnants of ICC networks. 5. Removal of the obstruction led to the redevelopment of ICC networks and recovery of slow wave activity within 30 days. Neural responses were partia lly restored in 30 days. 6. These data describe the plasticity of ICC networks in response to partia l obstruction. After obstruction the ICC phenotype was lost, but these cell s regenerated when the obstruction was removed. This model may be an import ant tool for evaluating the cellular/molecular factors responsible for the regulation and maintenance of the ICC phenotype.