Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon
- University of Nevada, Reno, United States
- Institute of Technology, Dundalk, Ireland
- University of Nevada, United States
Abstract
Interstitial cells of Cajal (ICC) generate pacemaker activity responsible for phasic contractions in colonic segmentation and peristalsis. ICC along the submucosal border (ICC-SM) contribute to mixing and more complex patterns of colonic motility. We show the complex patterns of Ca2+ signaling in ICC-SM and the relationship between ICC-SM Ca2+ transients and activation of SMCs using optogenetic tools. ICC-SM displayed rhythmic firing of Ca2+ transients ~15 cpm and paced adjacent SMCs. The majority of spontaneous activity occurred in regular Ca2+ transients clusters (CTCs) that propagated through the network. CTCs were organized and dependent upon Ca2+ entry through voltage-dependent Ca2+ conductances, L- and T-type Ca2+ channels. Removal of Ca2+ from the external solution abolished CTCs. Ca2+ release mechanisms reduced the duration and amplitude of Ca2+ transients but did not block CTCs. These data reveal how colonic pacemaker ICC-SM exhibit complex Ca2+ firing patterns and drive smooth muscle activity and overall colonic contractions.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK-120759)
- Salah A Baker
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK-120759)
- Kenton M Sanders
National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK-078736)
- Caroline A Cobine
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mark T Nelson, University of Vermont, United States
Ethics
Animal experimentation: The animals used, protocols performed and procedures in this study were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Use and Care Committee at the University of Nevada, Reno (IACUC; Protocol# 00053).
Version history
- Received: October 16, 2020
- Accepted: January 4, 2021
- Accepted Manuscript published: January 5, 2021 (version 1)
- Version of Record published: January 13, 2021 (version 2)
Copyright
© 2021, Baker et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon
eLife 10:e64099.
https://doi.org/10.7554/eLife.64099
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