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

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 Tim...

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Main Authors: Magali Cazade, Isabelle Bidaud, Philippe Lory, Jean Chemin
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-01-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/22331
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author Magali Cazade
Isabelle Bidaud
Philippe Lory
Jean Chemin
author_facet Magali Cazade
Isabelle Bidaud
Philippe Lory
Jean Chemin
author_sort Magali Cazade
collection DOAJ
description 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 a 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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spelling doaj.art-0fd9dfd2809a49318f11a36717ac3ca22022-12-22T04:32:39ZengeLife Sciences Publications LtdeLife2050-084X2017-01-01610.7554/eLife.22331Activity-dependent regulation of T-type calcium channels by submembrane calcium ionsMagali Cazade0Isabelle Bidaud1Philippe Lory2Jean Chemin3https://orcid.org/0000-0002-6089-5964IGF, CNRS, INSERM, University of Montpellier, Montpellier, France; LabEx 'Ion Channel Science and Therapeutics', Montpellier, FranceIGF, CNRS, INSERM, University of Montpellier, Montpellier, France; LabEx 'Ion Channel Science and Therapeutics', Montpellier, FranceIGF, CNRS, INSERM, University of Montpellier, Montpellier, France; LabEx 'Ion Channel Science and Therapeutics', Montpellier, FranceIGF, CNRS, INSERM, University of Montpellier, Montpellier, France; LabEx 'Ion Channel Science and Therapeutics', Montpellier, FranceVoltage-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 a 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.https://elifesciences.org/articles/22331low-voltage-activatedP2XTRP5-HTCav3.1Cav3.2
spellingShingle Magali Cazade
Isabelle Bidaud
Philippe Lory
Jean Chemin
Activity-dependent regulation of T-type calcium channels by submembrane calcium ions
eLife
low-voltage-activated
P2X
TRP
5-HT
Cav3.1
Cav3.2
title Activity-dependent regulation of T-type calcium channels by submembrane calcium ions
title_full Activity-dependent regulation of T-type calcium channels by submembrane calcium ions
title_fullStr Activity-dependent regulation of T-type calcium channels by submembrane calcium ions
title_full_unstemmed Activity-dependent regulation of T-type calcium channels by submembrane calcium ions
title_short Activity-dependent regulation of T-type calcium channels by submembrane calcium ions
title_sort activity dependent regulation of t type calcium channels by submembrane calcium ions
topic low-voltage-activated
P2X
TRP
5-HT
Cav3.1
Cav3.2
url https://elifesciences.org/articles/22331
work_keys_str_mv AT magalicazade activitydependentregulationofttypecalciumchannelsbysubmembranecalciumions
AT isabellebidaud activitydependentregulationofttypecalciumchannelsbysubmembranecalciumions
AT philippelory activitydependentregulationofttypecalciumchannelsbysubmembranecalciumions
AT jeanchemin activitydependentregulationofttypecalciumchannelsbysubmembranecalciumions