ICC-MY coordinate smooth muscle electrical and mechanical activity in the murine small intestine

Background Animals carrying genetic mutations have provided powerful insights into the role of interstitial cells of Cajal (ICC) in motility. One classic model is the W/WV mouse which carries loss-of-function mutations in c-kit alleles, but retains minimal function of the tyrosine kinase. Previous studies have documented loss of slow waves and aberrant motility in the small intestine of W/WV mice where myenteric ICC (ICC-MY) are significantly depleted. Methods Here, we used morphological and electrophysiological techniques to further assess the loss of ICC around the circumference of the small intestine and determine consequences of losing ICC-MY on electrical activity, Ca2+ transients and contractions of the longitudinal muscle (LM). Key Results In wild-type mice, there was coherent propagation of Ca2+ transients through the ICC-MY network and spread of this activity to the LM. In short segments of small intestine in vitro and in exteriorized segments, slow waves coordiated smoothly propagating Ca2+ waves and contractions in the LM of wild-type mice. In W/WV mice, Ca2+ waves were initiated at variable sites along and around intestinal segments and propagated without constraint unless they collided with other Ca2+ waves. This activity resulted in abrupt, uncoordinated contractions. Conclusions & Inferences These results show how dominance of pacemaking by ICC-MY coordinates propagating con-tractions and regulates the spontaneous activity of smooth muscle.