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Activity-dependent regulation of T-type calcium channels by submembrane calcium ions

  1. Magali Cazade
  2. Isabelle Bidaud
  3. Philippe Lory  Is a corresponding author
  4. Jean Chemin  Is a corresponding author
  1. IGF, CNRS, INSERM, Université de Montpellier, France
Research Article
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Cite this article as: eLife 2017;6:e22331 doi: 10.7554/eLife.22331


Voltage-gated Ca2+ channels are involved in numerous physiological functions and various mechanisms finely tune their activity, including the Ca2+ ion itself. This is well exemplified by the Ca2+-dependent inactivation of L-type Ca2+ channels, whose alteration contributes to the dramatic disease Timothy Syndrome. For T-type Ca2+ channels, a long-held view is that they are not regulated by intracellular Ca2+. Here we challenge this notion by using dedicated electrophysiological protocols on both native and expressed T-type Ca2+ channels. We demonstrate that a rise in submembrane Ca2+ induces a large decrease in T-type current amplitude due to an important hyperpolarizing shift in the steady-state inactivation. Activation of most representative Ca2+-permeable ionotropic receptors similarly regulate T-type current properties. Altogether, our data clearly establish that Ca2+ entry exerts a feedback control on T-type channel activity, by modulating the channel availability, a mechanism that critically links cellular properties of T-type Ca2+ channels to their physiological roles.

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Author details

  1. Magali Cazade

    IGF, CNRS, INSERM, Université de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Isabelle Bidaud

    IGF, CNRS, INSERM, Université de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Philippe Lory

    IGF, CNRS, INSERM, Université de Montpellier, Montpellier, France
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
  4. Jean Chemin

    IGF, CNRS, INSERM, Université de Montpellier, Montpellier, France
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6089-5964


Agence Nationale de la Recherche (ANR-10-BLAN-1601)

  • Philippe Lory

Laboratory of excellence in Ion Channel Science and Therapeutics (LabEx ICST)

  • Philippe Lory

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


Animal experimentation: All animal use procedures were done in accordance with the directives of the French Ministry of Agriculture (A 34-172-41).

Reviewing Editor

  1. Baron Chanda, University of Wisconsin-Madison, United States

Publication history

  1. Received: October 13, 2016
  2. Accepted: January 20, 2017
  3. Accepted Manuscript published: January 21, 2017 (version 1)
  4. Version of Record published: February 14, 2017 (version 2)


© 2017, Cazade 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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