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https://hdl.handle.net/2440/61090
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Type: | Journal article |
Title: | The first intestinal motility patterns in fetal mice are not mediated by neurons or interstitial cells of Cajal |
Author: | Roberts, R. Ellis, M. Gwynne, R. Bergner, A. Lewis, M. Spencer, E. Bornstein, J. Young, H. |
Citation: | The Journal of Physiology, 2010; 588(7):1153-1169 |
Publisher: | Blackwell Publishing Ltd |
Issue Date: | 2010 |
ISSN: | 0022-3751 1469-7793 |
Statement of Responsibility: | Rachael R. Roberts, Melina Ellis, Rachel M. Gwynne, Annette J. Bergner, Martin D. Lewis, Elizabeth A. Beckett, Joel C. Bornstein and Heather M. Young |
Abstract: | In mature animals, neurons and interstitial cells of Cajal (ICC) are essential for organized intestinal motility. We investigated motility patterns, and the roles of neurons and myenteric ICC (ICC-MP), in the duodenum and colon of developing mice in vitro. Spatiotemporal mapping revealed regular contractions that propagated in both directions from embryonic day (E)13.5 in the duodenum and E14.5 in the colon. The propagating contractions, which we termed ripples, were unaffected by tetrodotoxin and were present in the intestine of embryonic Ret null mutant mice, which lack enteric neurons. Neurally mediated motility patterns were first observed in the duodenum at E18.5. To examine the possible role of ICC-MP, three approaches were used. First, intracellular recordings from the circular muscle of the duodenum did not detect slow wave activity at E16.5, but regular slow waves were observed in some preparations of E18.5 duodenum. Second, spatiotemporal mapping revealed ripples in the duodenum of E13.5 and E16.5 W/Wv embryos, which lack KIT+ ICC-MP and slow waves. Third, KIT-immunoreactive cells with the morphology of ICC-MP were first observed at E18.5. Hence, ripples do not appear to be mediated by ICC-MP and must be myogenic. Ripples in the duodenum and colon were abolished by cobalt chloride (1 mm). The L-type Ca2+ channel antagonist nicardipine (2.5 μm) abolished ripples in the duodenum and reduced their frequency and size in the colon. Our findings demonstrate that prominent propagating contractions (ripples) are present in the duodenum and colon of fetal mice. Ripples are not mediated by neurons or ICC-MP, but entry of extracellular Ca2+ through L-type Ca2+ channels is essential. Thus, during development of the intestine, the first motor patterns to develop are myogenic. |
Keywords: | Colon Duodenum Neurons Myenteric Plexus Fetus Animals Mice Mice, Mutant Strains Cobalt Nicardipine Tetrodotoxin Calcium Channels, L-Type Gastrointestinal Motility Muscle Contraction Female Male Proto-Oncogene Proteins c-kit Interstitial Cells of Cajal |
Rights: | © 2010 The Authors. Journal compilation © 2010 The Physiological Society |
DOI: | 10.1113/jphysiol.2009.185421 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/454351 http://purl.org/au-research/grants/nhmrc/565319 http://purl.org/au-research/grants/arc/DP0878755 |
Published version: | http://dx.doi.org/10.1113/jphysiol.2009.185421 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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