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Although common risk factors underlie AF onset, in 15% of the affected population, AF may have a genetic cause. Here, we investigated how LMNA variants cause cardiac arrhythmicity. Drosophila melanogaster strains were generated possessing the analogous variants in the Drosophila orthologue of human lamin A\/C (LMNA), Lamin C (LamC). Heart wall movements in prepupae were recorded before (BTP) and after (ATP) tachypacing. ATP, flies expressing wild-type LamC, and the variants \u0394N and p.R205W showed a significant reduction in heart rate (HR), but the arrhythmia index (AI) was not affected, compared to BTP. By contrast, those expressing p.N210K and p.R264Q showed a significant reduction in HR and increased AI, compared to BTP. p.N210K- and p.R264Q-expressing prepupae showed contrasting effects after pharmacological intervention with microtubule stabilizer taxol. Taxol attenuated the arrhythmogenicity in p.N210K-expressing prepupae, but aggravated it in p.R264Q-expressing prepupae. These findings suggest that different lamin variants trigger distinct molecular pathways that drive arrhythmogenic effects in Drosophila.<\/jats:p>","DOI":"10.1242\/dmm.052424","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T03:32:22Z","timestamp":1751513542000},"source":"Crossref","is-referenced-by-count":0,"title":["Lamin variants cause cardiac arrhythmogenicity in <i>Drosophila<\/i>"],"prefix":"10.1242","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2921-936X","authenticated-orcid":false,"given":"Stan W.","family":"van Wijk","sequence":"first","affiliation":[{"name":"Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cardiovascular Sciences, Heart Failure and Arrhythmias 1 Department of Physiology , , 1081 HZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Puck","family":"Vree","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cardiovascular Sciences, Heart Failure and Arrhythmias 1 Department of Physiology , , 1081 HZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabries G.","family":"Huiskes","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cardiovascular Sciences, Heart Failure and Arrhythmias 1 Department of Physiology , , 1081 HZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinier L.","family":"van der Palen","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cardiovascular Sciences, Heart Failure and Arrhythmias 1 Department of Physiology , , 1081 HZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiste","family":"Liutkute","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University Medical Center G\u00f6ttingen 2 , 37075 G\u00f6ttingen ,","place":["Germany"]},{"name":"DZHK (German Center for Cardiovascular Research) 3 , Partner Site Lower Saxony, 37075 G\u00f6ttingen ,","place":["Germany"]},{"name":"Cluster of Excellence \u201cMultiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells\u201d (MBExC), University of G\u00f6ttingen 4 , 37075 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels","family":"Voigt","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University Medical Center G\u00f6ttingen 2 , 37075 G\u00f6ttingen ,","place":["Germany"]},{"name":"DZHK (German Center for Cardiovascular Research) 3 , Partner Site Lower Saxony, 37075 G\u00f6ttingen ,","place":["Germany"]},{"name":"Cluster of Excellence \u201cMultiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells\u201d (MBExC), University of G\u00f6ttingen 4 , 37075 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lori L.","family":"Wallrath","sequence":"additional","affiliation":[{"name":"University of Iowa 5 Department of Biochemistry and Molecular Biology , , Iowa City, IA 52242 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4768-234X","authenticated-orcid":false,"given":"Bianca J. J. M.","family":"Brundel","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cardiovascular Sciences, Heart Failure and Arrhythmias 1 Department of Physiology , , 1081 HZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"2025072505233812900_DMM052424C1","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/323560a0","article-title":"The nuclear lamina is a meshwork of intermediate-type filaments","volume":"323","author":"Aebi","year":"1986","journal-title":"Nature"},{"key":"2025072505233812900_DMM052424C2","doi-asserted-by":"publisher","first-page":"3757","DOI":"10.1038\/s41467-019-11684-x","article-title":"Structural basis for lamin assembly at the molecular level","volume":"10","author":"Ahn","year":"2019","journal-title":"Nat. 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