Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression
| Autor: | Yoshitaka Fujihara, Tomoaki Niimi, Tomomi Minemura, Shun'ichi Kuroda, Koichi Takimoto, Sébastien Wälchli, Jumpei Ito, Andrés D. Maturana |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Genetically modified mouse chemistry.chemical_element Mice Transgenic cardiomyocytes 030204 cardiovascular system & hematology Calcium DNA-binding protein Article Catalysis Muscle hypertrophy lcsh:Chemistry Inorganic Chemistry Calcium Channels T-Type 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Myocytes Cardiac Physical and Theoretical Chemistry lcsh:QH301-705.5 Molecular Biology Cells Cultured Spectroscopy Inhibitor of Differentiation Protein 2 aldosterone Aldosterone Organic Chemistry T-type calcium channel Cardiac arrhythmia Heart General Medicine Computer Science Applications Cell biology T-type calcium channels (List three to ten pertinent keywords specific to the article yet reasonably common within the subject discipline.) 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Gene Expression Regulation chemistry Sirna knockdown |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 7 International Journal of Molecular Sciences, Vol 22, Iss 3561, p 3561 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22073561 |
| Popis: | 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 (Ca2+) 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 Ca2+ channel) or CaV3.1, and CaV3.2 (T-type Ca2+ channels) mRNA expression levels and Ca2+ 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 Ca2+ 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. |
| Databáze: | OpenAIRE |
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