Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon

  1. Salah A Baker  Is a corresponding author
  2. Wesley A Leigh
  3. Guillermo Del Valle
  4. Inigo F De Yturriaga
  5. Sean M Ward
  6. Caroline A Cobine
  7. Bernard T Drumm
  8. Kenton M Sanders
  1. University of Nevada, Reno, United States
  2. Institute of Technology, Dundalk, Ireland
  3. 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.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Salah A Baker

    Physiology and Cell Biology, University of Nevada, Reno, Reno, United States
    For correspondence
    sabubaker@med.unr.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1514-6876
  2. Wesley A Leigh

    Physiology and Cell Biology, University of Nevada, Reno, Reno, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Guillermo Del Valle

    Physiology and Cell Biology, University of Nevada, Reno, Reno, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Inigo F De Yturriaga

    Physiology and Cell Biology, University of Nevada, Reno, Reno, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sean M Ward

    Physiology and Cell Biology, University of Nevada, Reno, Reno, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Caroline A Cobine

    Physiology and Cell Biology, University of Nevada, Reno, Reno, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Bernard T Drumm

    Department of Life & Health Science,, Institute of Technology, Dundalk, Dundalk, Ireland
    Competing interests
    The authors declare that no competing interests exist.
  8. Kenton M Sanders

    Physiology and Cell Biology, University of Nevada, Reno, United States
    Competing interests
    The authors declare that no competing interests exist.

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.

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).

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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https://doi.org/10.7554/eLife.64099

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