Experimental Antiarrhythmic Targets: CaMKII Inhibition – Ready for Clinical Evaluation?

Lars   S.   Maier

doi:10.2174/09298673113209990171

Abstract

In the recent years, Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) was suggested to be associated with cardiac hypertrophy and heart failure but also with arrhythmias both in animal models as well as in the human heart. This article focuses on the role of CaMKII for excitation-contraction coupling but more explicitly it highlights major CaMKIIdependent proarrhythmogenic mechanisms including SR Ca²⁺ leak and late Na⁺ current. Because a clinical significance of CaMKII is implied for both mechanisms, CaMKII inhibition is suggested to be a therapeutical approach in the near future.

Keywords: Arrhythmia, atrial fibrillation, Ca²⁺/calmodulin (Ca²⁺/CaM), Ca²⁺/CaM-dependent protein kinase II (CaMKII), excitation- contraction coupling (ECC), heart failure, hypertrophy, late Na⁺ current (I_Na, late), sarcoplasmic reticulum (SR), SR Ca²⁺ leak.