Activity-induced Ca2+ signaling in perisynaptic Schwann cells of the early postnatal mouse is mediated by P2Y1 receptors and regulates muscle fatigue

  1. Dante J Heredia
  2. Cheng-Yuan Feng
  3. Grant W Hennig
  4. Robert B Renden
  5. Thomas W Gould  Is a corresponding author
  1. University of Nevada School of Medicine, United States

Abstract

Perisynaptic glial cells respond to neural activity by increasing cytosolic calcium, but the significance of this pathway is unclear. Terminal/perisynaptic Schwann cells (TPSCs) are a perisynaptic glial cell at the neuromuscular junction that respond to nerve-derived substances such as acetylcholine and purines. Here, we provide genetic evidence that activity-induced calcium accumulation in neonatal TPSCs is mediated exclusively by one subtype of metabotropic purinergic receptor. In P2ry1 mutant mice lacking these responses, postsynaptic, rather than presynaptic, function was altered in response to nerve stimulation. This impairment was correlated with a greater susceptibility to activity-induced muscle fatigue. Interestingly, fatigue in P2ry1 mutants was more greatly exacerbated by exposure to high potassium than in control mice. High potassium itself increased cytosolic levels of calcium in TPSCs, a response which was also reduced P2ry1 mutants. These results suggest that activity-induced calcium responses in TPSCs regulate postsynaptic function and muscle fatigue by regulating perisynaptic potassium.

Article and author information

Author details

  1. Dante J Heredia

    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Cheng-Yuan Feng

    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3278-9451
  3. Grant W Hennig

    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Robert B Renden

    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Thomas W Gould

    Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, United States
    For correspondence
    tgould@medicine.nevada.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2154-9388

Funding

National Institute of General Medical Sciences (GM103554)

  • Thomas W Gould

National Center for Research Resources (5P20RR018751)

  • Grant W Hennig

National Institute of General Medical Sciences (GM110767)

  • Thomas W Gould

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (#00-666) of the University of Nevada School of Medicine. The University is fully accredited by AAALAC International.

Reviewing Editor

  1. Klaus-Armin Nave, Max-Planck-Institute for Experimental Medicine, Germany

Publication history

  1. Received: July 28, 2017
  2. Accepted: January 9, 2018
  3. Accepted Manuscript published: January 31, 2018 (version 1)
  4. Version of Record published: February 5, 2018 (version 2)

Copyright

© 2018, Heredia 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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  1. Dante J Heredia
  2. Cheng-Yuan Feng
  3. Grant W Hennig
  4. Robert B Renden
  5. Thomas W Gould
(2018)
Activity-induced Ca2+ signaling in perisynaptic Schwann cells of the early postnatal mouse is mediated by P2Y1 receptors and regulates muscle fatigue
eLife 7:e30839.
https://doi.org/10.7554/eLife.30839

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