Kit mutants and gastrointestinal physiology
- 21 December 2006
- journal article
- review article
- Published by Wiley in Journal Of Physiology-London
- Vol. 578 (1), 33-42
- https://doi.org/10.1113/jphysiol.2006.122473
Abstract
There has been considerable speculation about the function of interstitial cells of Cajal (ICC) since their discovery more than 100 years ago. It has been difficult to study these cells under native conditions, but great insights about the function of ICC have come from studies of genetic models with loss-of function mutations in the Kit signalling pathway. First it was discovered that signalling via Kit (a receptor tyrosine kinase) was vital for the development and maintenance of the ICC phenotype in gastrointestinal (GI) muscles. In compound heterozygotes (W/W(V) and Sl/Sl(d) animals), where there are partial loss-of-function mutations in Kit receptors or Kit ligand (stem cell factor), ICC failed to develop in various regions of the GI tract, but no major changes in the smooth muscle layers or enteric nervous system occurred in the absence of these cells. Animals with these mutations provided an unprecedented opportunity to understand the role of ICC in GI motor function, and it is now clear from these studies that ICC serve as: (i) pacemaker cells, generating the spontaneous electrical rhythms of the gut known as slow waves; (ii) a propagation pathway for slow waves so that large areas of the musculature can be entrained to a dominant pacemaker frequency; (iii) mediators of excitatory cholinergic and inhibitory nitrergic neural inputs from the enteric nervous system, and (iv) stretch receptors that modulate membrane potential and electrical slow wave frequency. This review describes the use of genetic models to understand the important physiological role of ICC in the GI tract.This publication has 82 references indexed in Scilit:
- Differential gene expression and functional analysis implicate novel mechanisms in enteric nervous system precursor migration and neuritogenesisDevelopmental Biology, 2006
- Properties of Pacemaker Potentials Recorded from Myenteric Interstitial Cells of Cajal Distributed in the Mouse Small IntestineJournal Of Physiology-London, 2003
- Excitation of smooth muscles isolated from the guinea‐pig gastric antrum in response to depolarizationJournal Of Physiology-London, 2002
- Selective loss of vagal intramuscular mechanoreceptors in mice mutant for steel factor, the c-Kit receptor ligandBrain Structure and Function, 2002
- Regional variation in contribution of myenteric and intramuscular interstitial cells of Cajal to generation of slow waves in mouse gastric antrumJournal Of Physiology-London, 2002
- Identification of rhythmically active cells in guinea‐pig stomachJournal Of Physiology-London, 1999
- Dissociation between electrical and mechanical responses to nitrergic stimulation in the canine gastric fundusJournal Of Physiology-London, 1998
- HPC-1/Syntaxin-1A Activity in the Enteric Nervous System of Developing Rat Gastrointestinal Tract.Journal of Smooth Muscle Research, 1997
- Heterogeneity in electrical activity of the canine ileal circular muscle: interaction of two pacemakersNeurogastroenterology & Motility, 1996
- Direct regulation of smooth muscle contractile elements by second messengersBiochemical and Biophysical Research Communications, 1989