{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T23:23:23Z","timestamp":1770679403961,"version":"3.49.0"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SANOFI R&amp;D"},{"name":"Fond Marion Elisabeth Brancher"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Arrhythmogenic cardiomyopathy (ACM) is a rare genetic disease associated with ventricular arrhythmias in patients. The occurrence of these arrhythmias is due to direct electrophysiological remodeling of the cardiomyocytes, namely a reduction in the action potential duration (APD) and a disturbance of Ca2+ homeostasis. Interestingly, spironolactone (SP), a mineralocorticoid receptor antagonist, is known to block K+ channels and may reduce arrhythmias. Here, we assess the direct effect of SP and its metabolite canrenoic acid (CA) in cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) of a patient bearing a missense mutation (c.394C&gt;T) in the DSC2 gene coding for desmocollin 2 and for the amino acid replacement of arginine by cysteine at position 132 (R132C). SP and CA corrected the APD in the muted cells (vs. the control) in linking to a normalization of the hERG and KCNQ1 K+ channel currents. In addition, SP and CA had a direct cellular effect on Ca2+ homeostasis. They reduced the amplitude and aberrant Ca2+ events. In conclusion, we show the direct beneficial effects of SP on the AP and Ca2+ homeostasis of DSC2-specific hiPSC-CMs. These results provide a rationale for a new therapeutical approach to tackle mechanical and electrical burdens in patients suffering from ACM.<\/jats:p>","DOI":"10.3390\/jpm13020335","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T05:12:26Z","timestamp":1676437946000},"page":"335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Spironolactone as a Potential New Treatment to Prevent Arrhythmias in Arrhythmogenic Cardiomyopathy Cell Model"],"prefix":"10.3390","volume":"13","author":[{"given":"Jean-Baptiste","family":"Reisqs","sequence":"first","affiliation":[{"name":"Neuromyogene Institute, Claude Bernard University, Lyon 1, 69008 Villeurbanne, France"},{"name":"PhyMedExp, INSERM, University of Montpellier, CNRS, 34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrien","family":"Moreau","sequence":"additional","affiliation":[{"name":"PhyMedExp, INSERM, University of Montpellier, CNRS, 34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1550-8945","authenticated-orcid":false,"given":"Yvonne","family":"Sleiman","sequence":"additional","affiliation":[{"name":"PhyMedExp, INSERM, University of Montpellier, CNRS, 34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azzouz","family":"Charrabi","sequence":"additional","affiliation":[{"name":"PhyMedExp, INSERM, University of Montpellier, CNRS, 34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Delini\u00e8re","sequence":"additional","affiliation":[{"name":"Service de Rythmologie, Hospices Civils de Lyon, 69500 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Bessi\u00e8re","sequence":"additional","affiliation":[{"name":"Service de Rythmologie, Hospices Civils de Lyon, 69500 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9203-4544","authenticated-orcid":false,"given":"Kevin","family":"Gardey","sequence":"additional","affiliation":[{"name":"Service de Rythmologie, Hospices Civils de Lyon, 69500 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9460-6705","authenticated-orcid":false,"given":"Sylvain","family":"Richard","sequence":"additional","affiliation":[{"name":"PhyMedExp, INSERM, University of Montpellier, CNRS, 34000 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Chevalier","sequence":"additional","affiliation":[{"name":"Neuromyogene Institute, Claude Bernard University, Lyon 1, 69008 Villeurbanne, France"},{"name":"Service de Rythmologie, Hospices Civils de Lyon, 69500 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/ncpcardio1182","article-title":"Mechanisms of disease: Molecular genetics of arrhythmogenic right ventricular dysplasia\/cardiomyopathy","volume":"5","author":"Awad","year":"2008","journal-title":"Nat. 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