biostudies-literatureLiu MNHLBI NIH HHS443-451https://www.ebi.ac.uk/biostudies/studies/S-EPMC9149111biostudies-literatureUnknown28(6)Cardiomyopathies are associated with arrhythmias and cardiac ion channel downregulation. This downregulation is arrhythmogenic. Paradoxically, antiarrhythmic therapies are based on ion channel-blocking drugs that further downregulate these channels and exhibit proarrhythmic risk. Recent studies have shown that inhibition of the protein kinase RNA-like ER kinase (PERK) arm of the unfolded protein response (UPR) prevents select cardiac ion channel downregulation and plays a protective role against arrhythmias. Prevention of ion channel downregulation represents as a novel therapeutic strategy to treat arrhythmias in myocardial infarction and heart failure.Trends in molecular medicinePreventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias.PMC9149111R01 HL104025Kang GJLiu MDudley SCfalsePreventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias.Cardiomyopathies are associated with arrhythmias and cardiac ion channel downregulation. This downregulation is arrhythmogenic. Paradoxically, antiarrhythmic therapies are based on ion channel-blocking drugs that further downregulate these channels and exhibit proarrhythmic risk. Recent studies have shown that inhibition of the protein kinase RNA-like ER kinase (PERK) arm of the unfolded protein response (UPR) prevents select cardiac ion channel downregulation and plays a protective role against arrhythmias. Prevention of ion channel downregulation represents as a novel therapeutic strategy to treat arrhythmias in myocardial infarction and heart failure.2022-01-01T00:00:00Z2022 Jun2025-04-04T21:07:45.216Z2025-04-04T21:07:45.216ZS-EPMC91491113541447810.1016/j.molmed.2022.03.006