{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:03:27Z","timestamp":1760148207956,"version":"build-2065373602"},"reference-count":77,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF18OC0052021","NNF19OC0056371"],"award-info":[{"award-number":["NNF18OC0052021","NNF19OC0056371"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Two \u03b1-isoforms of the Na+,K+-ATPase (\u03b11 and \u03b12) are expressed in the cardiovascular system, and it is unclear which isoform is the preferential regulator of contractility. Mice heterozygous for the familial hemiplegic migraine type 2 (FHM2) associated mutation in the \u03b12-isoform (G301R; \u03b12+\/G301R mice) have decreased expression of cardiac \u03b12-isoform but elevated expression of the \u03b11-isoform. We aimed to investigate the contribution of the \u03b12-isoform function to the cardiac phenotype of \u03b12+\/G301R hearts. We hypothesized that \u03b12+\/G301R hearts exhibit greater contractility due to reduced expression of cardiac \u03b12-isoform. Variables for contractility and relaxation of isolated hearts were assessed in the Langendorff system without and in the presence of ouabain (1 \u00b5M). Atrial pacing was performed to investigate rate-dependent changes. The \u03b12+\/G301R hearts displayed greater contractility than WT hearts during sinus rhythm, which was rate-dependent. The inotropic effect of ouabain was more augmented in \u03b12+\/G301R hearts than in WT hearts during sinus rhythm and atrial pacing. In conclusion, cardiac contractility was greater in \u03b12+\/G301R hearts than in WT hearts under resting conditions. The inotropic effect of ouabain was rate-independent and enhanced in \u03b12+\/G301R hearts, which was associated with increased systolic work.<\/jats:p>","DOI":"10.3390\/cells12081108","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:15:57Z","timestamp":1681096557000},"page":"1108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hypercontractile Cardiac Phenotype in Mice with Migraine-Associated Mutation in the Na+,K+-ATPase \u03b12-Isoform"],"prefix":"10.3390","volume":"12","author":[{"given":"Rajkumar","family":"Rajanathan","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e0udia Vilaseca i","family":"Riera","sequence":"additional","affiliation":[{"name":"Department of Basic Science, School of Medicine and Health Sciences, International University of Catalonia, 08195 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7950-4647","authenticated-orcid":false,"given":"Tina Myhre","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5431-4409","authenticated-orcid":false,"given":"Christian","family":"Staehr","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena V.","family":"Bouzinova","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens Randel","family":"Nyengaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Core Center for Molecular Morphology, Section for Stereology and Microscopy, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Department of Pathology, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten B.","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Biomedical Sciences, University of Copenhagen, 1168 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6358-8962","authenticated-orcid":false,"given":"Hans Erik","family":"B\u00f8tker","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3303-1095","authenticated-orcid":false,"given":"Vladimir V.","family":"Matchkov","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1016\/j.jacc.2019.10.009","article-title":"The Global Burden of Cardiovascular Diseases and Risk Factors","volume":"74","author":"Fuster","year":"2019","journal-title":"J. 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