CaMKII as a target for arrhythmia suppression

Pharmacol Ther. 2017 Aug:176:22-31. doi: 10.1016/j.pharmthera.2016.10.006. Epub 2016 Oct 11.

Abstract

Calcium/calmodulin-dependent protein kinase II (CaMKII) has emerged as key enzyme in many cardiac pathologies, especially heart failure (HF), myocardial infarction and cardiomyopathies, thus leading to contractile dysfunction and malignant arrhythmias. While many pathways leading to CaMKII activation have been elucidated in recent years, hardly any clinically viable compounds affecting CaMKII activity have progressed from basic in vitro science to in vivo studies. This review focuses on recent advances in anti-arrhythmic strategies involving CaMKII. Specifically, both inhibition of CaMKII itself to prevent arrhythmias, as well as anti-arrhythmic approaches affecting CaMKII activity via alterations in signaling cascades upstream and downstream of CaMKII will be discussed.

Keywords: Arrhythmias; CaMKII; Calcium leak; Excitation–contraction coupling; Inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / pharmacology
  • Anti-Arrhythmia Agents / therapeutic use*
  • Arrhythmias, Cardiac / drug therapy*
  • Arrhythmias, Cardiac / metabolism
  • Arrhythmias, Cardiac / physiopathology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / physiology
  • Humans

Substances

  • Anti-Arrhythmia Agents
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2