Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias.
- Resource Type
- Article
- Authors
- Liu, Man; Kang, Gyeoung-Jin; Dudley, Samuel C.
- Source
- Trends in Molecular Medicine. Jun2022, Vol. 28 Issue 6, p443-451. 9p.
- Subject
- *ION channels
*ARRHYTHMIA
*UNFOLDED protein response
*MYOCARDIAL infarction
*PROTEIN kinases
*HEART failure
- Language
- ISSN
- 1471-4914
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. Cardiac ion channels are often downregulated in cardiomyopathies and this downregulation contributes to lethal arrhythmias. Current treatments for arrhythmias with ion channel blocking drugs are proarrhythmic. Activation of the unfolded protein response (UPR) in cardiomyopathies contributes to the downregulation of cardiac ion channels Inhibiting the protein kinase RNA-like ER kinase (PERK) arm of UPR can prevent ion channel downregulation and is antiarrhythmic. Preventing ion channel downregulation can reduce arrhythmic risk with no proarrhythmic potential and represents a new treatment paradigm. [ABSTRACT FROM AUTHOR]