Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias

Trends Mol Med. 2022 Jun;28(6):443-451. doi: 10.1016/j.molmed.2022.03.006. Epub 2022 Apr 10.

Abstract

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.

Keywords: cardiac ion channel; heart failure; mRNA degradation; myocardial infarction; therapy.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Arrhythmia Agents / pharmacology
  • Anti-Arrhythmia Agents / therapeutic use
  • Arrhythmias, Cardiac* / drug therapy
  • Arrhythmias, Cardiac* / etiology
  • Arrhythmias, Cardiac* / metabolism
  • Humans
  • Ion Channels / metabolism
  • Ion Channels / therapeutic use
  • Myocardial Infarction*
  • Unfolded Protein Response

Substances

  • Anti-Arrhythmia Agents
  • Ion Channels