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Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression

Aldosterone excess is a cardiovascular risk factor. Aldosterone can directly stimulate an electrical remodeling of cardiomyocytes leading to cardiac arrhythmia and hypertrophy. L-type and T-type voltage-gated calcium (Ca(2+)) channels expression are increased by aldosterone in cardiomyocytes. To fur...

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Autores principales: Ito, Jumpei, Minemura, Tomomi, Wälchli, Sébastien, Niimi, Tomoaki, Fujihara, Yoshitaka, Kuroda, Shun’ichi, Takimoto, Koichi, Maturana, Andrés D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037527/
https://www.ncbi.nlm.nih.gov/pubmed/33808082
http://dx.doi.org/10.3390/ijms22073561
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author Ito, Jumpei
Minemura, Tomomi
Wälchli, Sébastien
Niimi, Tomoaki
Fujihara, Yoshitaka
Kuroda, Shun’ichi
Takimoto, Koichi
Maturana, Andrés D.
author_facet Ito, Jumpei
Minemura, Tomomi
Wälchli, Sébastien
Niimi, Tomoaki
Fujihara, Yoshitaka
Kuroda, Shun’ichi
Takimoto, Koichi
Maturana, Andrés D.
author_sort Ito, Jumpei
collection PubMed
description Aldosterone excess is a cardiovascular risk factor. Aldosterone can directly stimulate an electrical remodeling of cardiomyocytes leading to cardiac arrhythmia and hypertrophy. L-type and T-type voltage-gated calcium (Ca(2+)) channels expression are increased by aldosterone in cardiomyocytes. To further understand the regulation of these channels expression, we studied the role of a transcriptional repressor, the inhibitor of differentiation/DNA binding protein 2 (Id2). We found that aldosterone inhibited the expression of Id2 in neonatal rat cardiomyocytes and in the heart of adult mice. When Id2 was overexpressed in cardiomyocytes, we observed a reduction in the spontaneous action potentials rate and an arrest in aldosterone-stimulated rate increase. Accordingly, Id2 siRNA knockdown increased this rate. We also observed that CaV1.2 (L-type Ca(2+) channel) or CaV3.1, and CaV3.2 (T-type Ca(2+) channels) mRNA expression levels and Ca(2+) currents were affected by Id2 presence. These observations were further corroborated in a heart specific Id2- transgenic mice. Taken together, our results suggest that Id2 functions as a transcriptional repressor for L- and T-type Ca(2+) channels, particularly CaV3.1, in cardiomyocytes and its expression is controlled by aldosterone. We propose that Id2 might contributes to a protective mechanism in cardiomyocytes preventing the presence of channels associated with a pathological state.
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spelling pubmed-80375272021-04-12 Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression Ito, Jumpei Minemura, Tomomi Wälchli, Sébastien Niimi, Tomoaki Fujihara, Yoshitaka Kuroda, Shun’ichi Takimoto, Koichi Maturana, Andrés D. Int J Mol Sci Article Aldosterone excess is a cardiovascular risk factor. Aldosterone can directly stimulate an electrical remodeling of cardiomyocytes leading to cardiac arrhythmia and hypertrophy. L-type and T-type voltage-gated calcium (Ca(2+)) channels expression are increased by aldosterone in cardiomyocytes. To further understand the regulation of these channels expression, we studied the role of a transcriptional repressor, the inhibitor of differentiation/DNA binding protein 2 (Id2). We found that aldosterone inhibited the expression of Id2 in neonatal rat cardiomyocytes and in the heart of adult mice. When Id2 was overexpressed in cardiomyocytes, we observed a reduction in the spontaneous action potentials rate and an arrest in aldosterone-stimulated rate increase. Accordingly, Id2 siRNA knockdown increased this rate. We also observed that CaV1.2 (L-type Ca(2+) channel) or CaV3.1, and CaV3.2 (T-type Ca(2+) channels) mRNA expression levels and Ca(2+) currents were affected by Id2 presence. These observations were further corroborated in a heart specific Id2- transgenic mice. Taken together, our results suggest that Id2 functions as a transcriptional repressor for L- and T-type Ca(2+) channels, particularly CaV3.1, in cardiomyocytes and its expression is controlled by aldosterone. We propose that Id2 might contributes to a protective mechanism in cardiomyocytes preventing the presence of channels associated with a pathological state. MDPI 2021-03-30 /pmc/articles/PMC8037527/ /pubmed/33808082 http://dx.doi.org/10.3390/ijms22073561 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Ito, Jumpei
Minemura, Tomomi
Wälchli, Sébastien
Niimi, Tomoaki
Fujihara, Yoshitaka
Kuroda, Shun’ichi
Takimoto, Koichi
Maturana, Andrés D.
Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression
title Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression
title_full Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression
title_fullStr Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression
title_full_unstemmed Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression
title_short Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression
title_sort id2 represses aldosterone-stimulated cardiac t-type calcium channels expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037527/
https://www.ncbi.nlm.nih.gov/pubmed/33808082
http://dx.doi.org/10.3390/ijms22073561
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