biostudies-literatureMarksteiner JAustrian Science Fund FWFLudwig Boltzmann GesellschaftLudwig Boltzmann Gesellschaft (LBG)H648-H660https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618084biostudies-literatureUnknown329(3)Cardiac arrhythmias significantly contribute to mortality in Duchenne muscular dystrophy (DMD), a severe muscle disease caused by dystrophin deficiency. Using the <i>mdx</i> mouse model for human DMD, we previously showed that the lack of dystrophin induces a significant loss of peak sodium current (<i>I</i>_Na) in ventricular cardiomyocytes. This provided a mechanistic explanation for ventricular conduction defects and concomitant arrhythmias in the dystrophic heart. The extracellular matrix protein tenascin C (TN-C), a major remodeling factor in the diseased heart, is strongly upregulated in DMD. The consequences of TN-C upregulation in the dystrophic heart, however, are unknown. Here, we tested if TN-C induces electrical remodeling in the dystrophic heart, and if inhibition ofAmerican journal of physiology. Heart and circulatory physiologyInhibition of tenascin C rescues abnormally reduced Na currents in dystrophin-deficient ventricular cardiomyocytes.PMC7618084P 35878P 35542CARREM Project Line2020-2024P35878-BP35542-BHackl BSzabo PLSchicker KKiss AKoenig XDavid FOSchindler NDostal CHilber KTodt HPodesser BKSauer JLilliu EMarksteiner JHohenegger MfalseInhibition of tenascin C rescues abnormally reduced Na currents in dystrophin-deficient ventricular cardiomyocytes.Cardiac arrhythmias significantly contribute to mortality in Duchenne muscular dystrophy (DMD), a severe muscle disease caused by dystrophin deficiency. Using the <i>mdx</i> mouse model for human DMD, we previously showed that the lack of dystrophin induces a significant loss of peak sodium current (<i>I</i>_Na) in ventricular cardiomyocytes. This provided a mechanistic explanation for ventricular conduction defects and concomitant arrhythmias in the dystrophic heart. The extracellular matrix protein tenascin C (TN-C), a major remodeling factor in the diseased heart, is strongly upregulated in DMD. The consequences of TN-C upregulation in the dystrophic heart, however, are unknown. Here, we tested if TN-C induces electrical remodeling in the dystrophic heart, and if inhibition of2025-01-01T00:00:00Z2025 Sep2026-06-02T20:28:18.099Z2026-04-20T03:09:59.714ZS-EPMC76180844078917710.1152/ajpheart.00307.2025