biostudies-literatureJimenez-Vazquez ENNational Institute of Arthritis and Musculoskeletal and Skin DiseasesDr. Bernard LublinNational Heart, Lung, and Blood InstituteNHLBI NIH HHSLa Caixa Banking FoundationHorizon 2020 - Research and Innovation Framework ProgrammeRappaport FoundationAmerican Heart AssociationInstituto de Salud Carlos IIIUS-Israel Binational Science FoundationFundación La Marató 2020Niedersachsen FoundationDuchenne Parent ProjectIsrael Science FoundationNIAMS NIH HHSe76576https://www.ebi.ac.uk/biostudies/studies/S-EPMC9239678biostudies-literatureUnknown11<h4>Background</h4>Patients with cardiomyopathy of Duchenne Muscular Dystrophy (DMD) are at risk of developing life-threatening arrhythmias, but the mechanisms are unknown. We aimed to determine the role of ion channels controlling cardiac excitability in the mechanisms of arrhythmias in DMD patients.<h4>Methods</h4>To test whether dystrophin mutations lead to defective cardiac Na_V1.5-Kir2.1 channelosomes and arrhythmias, we generated iPSC-CMs from two hemizygous DMD males, a heterozygous female, and two unrelated control males. We conducted studies including confocal microscopy, protein expression analysis, patch-clamping, non-viral piggy-bac gene expression, optical mapping and contractility assays.<h4>Results</h4>Two patients had abnormal ECGs with frequent runs of ventriculaeLife<i>SNTA1</i> gene rescues ion channel function and is antiarrhythmic in cardiomyocytes derived from induced pluripotent stem cells from muscular dystrophy patients.PMC9239678842/1901012020RI2013032ZN3452R01 AR068428736/C/2020LCF/PR/HR19/5216001319POST34380706sDonation2029771R01 HL122352PI20/012202019039AR068428GA-965286Cruz FMGuerrero-Serna GHerron TJJalife JMacias AMonteiro da Rocha AJimenez-Vazquez ENVera-Pedrosa MLGutierrez LKCuttitta AJPonce-Balbuena DMichele DEArad MBinah Ofalse<i>SNTA1</i> gene rescues ion channel function and is antiarrhythmic in cardiomyocytes derived from induced pluripotent stem cells from muscular dystrophy patients.<h4>Background</h4>Patients with cardiomyopathy of Duchenne Muscular Dystrophy (DMD) are at risk of developing life-threatening arrhythmias, but the mechanisms are unknown. We aimed to determine the role of ion channels controlling cardiac excitability in the mechanisms of arrhythmias in DMD patients.<h4>Methods</h4>To test whether dystrophin mutations lead to defective cardiac Na_V1.5-Kir2.1 channelosomes and arrhythmias, we generated iPSC-CMs from two hemizygous DMD males, a heterozygous female, and two unrelated control males. We conducted studies including confocal microscopy, protein expression analysis, patch-clamping, non-viral piggy-bac gene expression, optical mapping and contractility assays.<h4>Results</h4>Two patients had abnormal ECGs with frequent runs of ventricula2022-01-01T00:00:00Z2022 Jun2026-05-27T19:18:06.444Z2022-07-10T15:43:03.907ZS-EPMC92396783576221110.7554/eLife.76576