Korean Circ J.  2013 Mar;43(3):145-151. 10.4070/kcj.2013.43.3.145.

A Memory Molecule, Ca2+/Calmodulin-Dependent Protein Kinase II and Redox Stress; Key Factors for Arrhythmias in a Diseased Heart

• Song YH

• KMID: 2224956
• DOI: http://doi.org/10.4070/kcj.2013.43.3.145

Abstract

Arrhythmias can develop in various cardiac diseases, such as ischemic heart disease, cardiomyopathy and congenital heart disease. It can also contribute to the aggravation of heart failure and sudden cardiac death. Redox stress and Ca2+ overload are thought to be the important triggering factors in the generation of arrhythmias in failing myocardium. From recent studies, it appears evident that Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a central role in the arrhythmogenic processes in heart failure by sensing intracellular Ca2+ and redox stress, affecting individual ion channels and thereby leading to electrical instability in the heart. CaMKII, a multifunctional serine/threonine kinase, is an abundant molecule in the neuron and the heart. It has a specific property as "a memory molecule" such that the binding of calcified calmodulin (Ca2+/CaM) to the regulatory domain on CaMKII initially activates this enzyme. Further, it allows autophosphorylation of T287 or oxidation of M281/282 in the regulatory domain, resulting in sustained activation of CaMKII even after the dissociation of Ca2+/CaM. This review provides the understanding of both the structural and functional properties of CaMKII, the experimental findings of the interactions between CaMKII, redox stress and individual ion channels, and the evidences proving the potential participation of CaMKII and oxidative stress in the diverse arrhythmogenic processes in a diseased heart.

Keyword

Calcium-calmodulin-dependent protein kinase type 2; Oxidative stress; Arrhythmias cardiac; Heart failure

MeSH Terms

Arrhythmias, Cardiac
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calmodulin
Cardiomyopathies
Death, Sudden, Cardiac
Heart
Heart Diseases
Heart Failure
Ion Channels
Memory
Myocardial Ischemia
Myocardium
Neurons
Oxidation-Reduction
Oxidative Stress
Protein Kinases
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calmodulin
Ion Channels
Protein Kinases

Figure

• 

  Fig. 1 Binding of Ca2+/CaM initially activates CaMKII, and allows autophosphorylation and oxidation of target amino-acids in the regulatory domain, thereby leading to sustained activation of CaMKII, independently of Ca2+/CaM. CaMKII: Ca2+/calmodulin-dependent protein kinase II.

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