1. Cell Biology
  2. Computational and Systems Biology
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Highly Localized intracellular Ca2+ signals promote optimal salivary gland fluid secretion

  1. Takahiro Takano
  2. Amanda Wahl
  3. Kai-Ting Huang
  4. Takanori Narita
  5. John Rugis
  6. James Sneyd
  7. David I Yule  Is a corresponding author
  1. University of Rochester School of Medicine and Dentistry, United States
  2. U. Rochester, United States
  3. Nihon University, Japan
  4. University of Auckland, New Zealand
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Cite this article as: eLife 2021;10:e66170 doi: 10.7554/eLife.66170

Abstract

Salivary fluid secretion involves an intricate choreography of membrane transporters to result in the trans-epithelial movement of NaCl and water into the acinus lumen. Current models are largely based on experimental observations in enzymatically isolated cells where the Ca2+ signal invariably propagates globally and thus appears ideally suited to activate spatially separated Cl and K channels, present on the apical and basolateral plasma membrane, respectively. We monitored Ca2+ signals and salivary secretion in live mice expressing GCamp6F, following stimulation of the nerves innervating the submandibular gland. Consistent with in vitro studies, Ca2+ signals were initiated in the apical endoplasmic reticulum. In marked contrast to in vitro data, highly localized trains of Ca2+ transients that failed to fully propagate from the apical region were observed. Following stimuli optimum for secretion, large apical-basal gradients were elicited. A new mathematical model, incorporating these data was constructed to probe how salivary secretion can be optimally stimulated by apical Ca2+ signals.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2,3,4,5,6,9,10,11

Article and author information

Author details

  1. Takahiro Takano

    Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Amanda Wahl

    Pharmacology and Physiology, U. Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kai-Ting Huang

    Pharmacology and Physiology, U. Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Takanori Narita

    Nihon University, Fujisawa, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. John Rugis

    Mathematics, University of Auckland, Auckland, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8009-4152
  6. James Sneyd

    Mathematics, University of Auckland, Auckland, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  7. David I Yule

    Pharmacology and Physiology, U. Rochester, Rochester, United States
    For correspondence
    david_yule@urmc.rochester.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6743-0668

Funding

National Institute of Dental and Craniofacial Research (DE019245)

  • David I Yule

National Institute of Dental and Craniofacial Research (DE014756)

  • David I Yule

Marsden Fund

  • James Sneyd

National Institute of Dental and Craniofacial Research (F31 DE030670)

  • Amanda Wahl

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal procedures were approved by University Committee on Animal Resources (UCAR-2001-214E)

Reviewing Editor

  1. Richard S Lewis, Stanford University School of Medicine, United States

Publication history

  1. Received: December 31, 2020
  2. Accepted: July 8, 2021
  3. Accepted Manuscript published: July 9, 2021 (version 1)

Copyright

© 2021, Takano 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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