Reduced distribution of pacemaking cells in dilated colon
- 80 Downloads
Interstitial cells of Cajal (ICC) act as pacemaker in gastrointestinal smooth muscle. In animals, small bowel dilatation produces a reduction in ICC numbers and in pacemaker function. With resolution of dilatation, ICC numbers and pacemaking function are partially restored. In human colonic disease states, dilatation is associated with dysmotility. The effect of dilatation on ICC distribution has not previously been examined in the human colon. Tissues from a neonate with colonic atresia and a 17-year-old adolescent with acquired megasigmoid were fixed, sectioned and incubated with anti cKit antibodies followed by fluorescent secondary antibodies. Distended and non-distended segments of colon were examined for ICC distribution using immunohistochemistry to c-Kit. Images were obtained with confocal microscopy. In both patients, there was a marked reduction in cKit-immunoreactive cells in the circular muscle and the myenteric plexus of the distended colon compared to the distal non-distended colon. Dilatation of the human colon is associated with a marked reduction in ICC. A resulting loss of pacemaker function could contribute to dysmotility associated with distension. Further studies assessing pacemaking function in human subjects and investigating reversibility of ICC disruption may allow new therapeutic strategies.
KeywordsInterstitial cells of Cajal Colon Atresia Constipation Obstruction
- 4.Sanders KM, Ordog T, Ward SM (2002) Physiology and pathophysiology of the interstitial cells of Cajal: from bench to bedside. IV. Genetic and animal models of GI motility disorders caused by loss of interstitial cells of Cajal. Am J Physiol Gastrointest Liver Physiol 282(5):G747–G756PubMedGoogle Scholar