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...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
eLife Sciences Publications Ltd
2017-01-01
|
Series: | eLife |
Subjects: | |
Online Access: | https://elifesciences.org/articles/22331 |
_version_ | 1811180587433590784 |
---|---|
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. |
first_indexed | 2024-04-11T09:05:43Z |
format | Article |
id | doaj.art-0fd9dfd2809a49318f11a36717ac3ca2 |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-11T09:05:43Z |
publishDate | 2017-01-01 |
publisher | eLife Sciences Publications Ltd |
record_format | Article |
series | eLife |
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 |