Activity-dependent regulation of T-type calcium channels by submembrane calcium ions
Abstract
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.
Article and author information
Author details
Funding
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.
Reviewing Editor
- Baron Chanda, University of Wisconsin-Madison, United States
Ethics
Animal experimentation: All animal use procedures were done in accordance with the directives of the French Ministry of Agriculture (A 34-172-41).
Version history
- Received: October 13, 2016
- Accepted: January 20, 2017
- Accepted Manuscript published: January 21, 2017 (version 1)
- Version of Record published: February 14, 2017 (version 2)
Copyright
© 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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