{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:11:11Z","timestamp":1790655071473,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T00:00:00Z","timestamp":1538006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Activation of the mineralocorticoid receptor (MR) in the heart is considered to be a cardiovascular risk factor. MR activation leads to heart hypertrophy and arrhythmia. In ventricular cardiomyocytes, aldosterone induces a profound remodeling of ion channel expression, in particular, an increase in the expression and activity of T-type voltage-gated calcium channels (T-channels). The molecular mechanisms immediately downstream from MR activation, which lead to the increased expression of T-channels and, consecutively, to an acceleration of spontaneous cell contractions in vitro, remain poorly investigated. Here, we investigated the putative role of a specific microRNA in linking MR activation to the regulation of T-channel expression and cardiomyocyte beating frequency. A screening assay identified microRNA 204 (miR-204) as one of the major upregulated microRNAs after aldosterone stimulation of isolated neonatal rat cardiomyocytes. Aldosterone significantly increased the level of miR-204, an effect blocked by the MR antagonist spironolactone. When miR-204 was overexpressed in isolated cardiomyocytes, their spontaneous beating frequency was significantly increased after 24 h, like upon aldosterone stimulation, and messenger RNAs coding T-channels (CaV3.1 and CaV3.2) were increased. Concomitantly, T-type calcium currents were significantly increased upon miR-204 overexpression. Specifically repressing the expression of miR-204 abolished the aldosterone-induced increase of CaV3.1 and CaV3.2 mRNAs, as well as T-type calcium currents. Finally, aldosterone and miR-204 overexpression were found to reduce REST-NRSF, a known transcriptional repressor of CaV3.2 T-type calcium channels. Our study thus strongly suggests that miR-204 expression stimulated by aldosterone promotes the expression of T-channels in isolated rat ventricular cardiomyocytes, and therefore, increases the frequency of the cell spontaneous contractions, presumably through the inhibition of REST-NRSF protein.<\/jats:p>","DOI":"10.3390\/ijms19102941","type":"journal-article","created":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T02:54:54Z","timestamp":1538103294000},"page":"2941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["MicroRNA-204 Is Necessary for Aldosterone-Stimulated T-Type Calcium Channel Expression in Cardiomyocytes"],"prefix":"10.3390","volume":"19","author":[{"given":"Riko","family":"Koyama","sequence":"first","affiliation":[{"name":"Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiphaine","family":"Mannic","sequence":"additional","affiliation":[{"name":"Department of Human Protein Science, University of Geneva, CH-1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5149-9962","authenticated-orcid":false,"given":"Jumpei","family":"Ito","sequence":"additional","affiliation":[{"name":"Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Amar","sequence":"additional","affiliation":[{"name":"Inserm, UMRS_970, Paris Cardiovascular Research Center, 75015 Paris, France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, 75015 Paris, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Unit\u00e9 Hypertension art\u00e9rielle, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Christina","family":"Zennaro","sequence":"additional","affiliation":[{"name":"Inserm, UMRS_970, Paris Cardiovascular Research Center, 75015 Paris, France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, 75015 Paris, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Service de G\u00e9n\u00e9tique, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6193-6388","authenticated-orcid":false,"given":"Michel","family":"Rossier","sequence":"additional","affiliation":[{"name":"Department of Human Protein Science, University of Geneva, CH-1211 Geneva, Switzerland"},{"name":"Central Institute of Hospitals, Hospital of Valais, CH-1951 Sion, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Maturana","sequence":"additional","affiliation":[{"name":"Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17a","DOI":"10.1016\/0002-9149(93)90240-D","article-title":"Influence of arterial blood pressure and aldosterone on left ventricular hypertrophy in moderate essential hypertension","volume":"71","author":"Duprez","year":"1993","journal-title":"Am. 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