Distinct signatures of calcium activity in brain mural cells

  1. Chaim Glück  Is a corresponding author
  2. Kim David Ferrari
  3. Noemi Binini
  4. Annika Keller
  5. Aiman S Saab
  6. Jillian L Stobart
  7. Bruno Weber  Is a corresponding author
  1. University of Zurich, Switzerland
  2. Max-Planck-Institute for Experimental Medicine, Germany
  3. College of Pharmacy, Canada

Abstract

Pericytes have been implicated in various neuropathologies, yet, little is known about their function and signaling pathways in health. Here, we characterized calcium dynamics of cortical mural cells in anesthetized or awake Pdgfrb-CreERT2;Rosa26<LSL-GCaMP6s> mice and in acute brain slices. Smooth muscle cells (SMCs) and ensheathing pericytes (EPs), also named as terminal vascular SMCs, revealed similar calcium dynamics in vivo. In contrast, calcium signals in capillary pericytes (CPs) were irregular, higher in frequency and occurred in cellular microdomains. In the absence of the vessel constricting agent U46619 in acute slices, SMCs and EPs revealed only sparse calcium signals whereas CPs retained their spontaneous calcium activity. Interestingly, chemogenetic activation of neurons in vivo and acute elevations of extracellular potassium in brain slices strongly decreased calcium activity in CPs. We propose that neuronal activation and an extracellular increase in potassium suppress calcium activity in CPs, likely mediated by Kir2.2 and KATP channels.

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 and 6.

Article and author information

Author details

  1. Chaim Glück

    Institute of Pharmacology and Toxicology, University of Zurich, Zürich, Switzerland
    For correspondence
    chaim.glueck@uzh.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8754-9965
  2. Kim David Ferrari

    Institute of Pharmacology and Toxicology, University of Zurich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7565-1276
  3. Noemi Binini

    Institute of Pharmacology and Toxicology, University of Zurich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Annika Keller

    Dept. of Neurosurgery, University of Zurich, 8952/Schlieren, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1466-3633
  5. Aiman S Saab

    Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Jillian L Stobart

    Rady Faculty of Health Sciences, College of Pharmacy, Winnipeg, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Bruno Weber

    Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
    For correspondence
    bweber@pharma.uzh.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9089-0689

Ethics

Animal experimentation: All animal experiments were approved by the local Cantonal Veterinary Office inZürich (license ZH 169/17) and conformed to the guidelines of the Swiss Animal Protection Law, Swiss Veterinary Office, Canton of Zürich(Animal Welfare Act of 16 December 2005 and Animal Protection Ordinance of 23 April 2008). Every effort was made to minimize suffering andconform to the 3Rs principles.

Reviewing Editor

  1. Mark T Nelson, University of Vermont, United States

Publication history

  1. Received: May 21, 2021
  2. Accepted: June 15, 2021
  3. Accepted Manuscript published: July 6, 2021 (version 1)
  4. Accepted Manuscript updated: July 16, 2021 (version 2)
  5. Version of Record published: July 21, 2021 (version 3)

Copyright

© 2021, Glück 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. Chaim Glück
  2. Kim David Ferrari
  3. Noemi Binini
  4. Annika Keller
  5. Aiman S Saab
  6. Jillian L Stobart
  7. Bruno Weber
(2021)
Distinct signatures of calcium activity in brain mural cells
eLife 10:e70591.
https://doi.org/10.7554/eLife.70591
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