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/W(V) 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/W(V) 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, Ca(2+) transients and contractions of the longitudinal muscle (LM). KEY RESULTS: In wild-type mice, there was coherent propagation of Ca(2+) 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 coordinated smoothly propagating Ca(2+) waves and contractions in the LM of wild-type mice. In W/W(V) mice, Ca(2+) waves were initiated at variable sites along and around intestinal segments and propagated without constraint unless they collided with other Ca(2+) 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.
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/W(V) 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/W(V) 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, Ca(2+) transients and contractions of the longitudinal muscle (LM). KEY RESULTS: In wild-type mice, there was coherent propagation of Ca(2+) 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 coordinated smoothly propagating Ca(2+) waves and contractions in the LM of wild-type mice. In W/W(V) mice, Ca(2+) waves were initiated at variable sites along and around intestinal segments and propagated without constraint unless they collided with other Ca(2+) 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.
Authors: Adam Rich; Scott Gordon; Chris Brown; Simon J Gibbons; Katherine Schaefer; Grant Hennig; Gianrico Farrugia Journal: Zebrafish Date: 2013-01-08 Impact factor: 1.985
Authors: Evan R Ball; Miho M Matsuda; Louis Dye; Victoria Hoffmann; Patricia M Zerfas; Eva Szarek; Adam Rich; Ajay B Chitnis; Constantine A Stratakis Journal: Cell Tissue Res Date: 2012-05-25 Impact factor: 5.249
Authors: Wesley A Leigh; Guillermo Del Valle; Sharif Amit Kamran; Bernard T Drumm; Alireza Tavakkoli; Kenton M Sanders; Salah A Baker Journal: Cell Calcium Date: 2020-07-28 Impact factor: 6.817
Authors: Jorge A Castorena-Gonzalez; Scott D Zawieja; Min Li; R Sathish Srinivasan; Alexander M Simon; Cor de Wit; Roger de la Torre; Luis A Martinez-Lemus; Grant W Hennig; Michael J Davis Journal: Circ Res Date: 2018-09-28 Impact factor: 17.367