title: A Memory Molecule, Ca(2+)/Calmodulin-Dependent Protein Kinase II and Redox Stress; Key Factors for Arrhythmias in a Diseased Heart.
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 Ca(2+) overload are thought to be the important triggering factors in the generation of arrhythmias in failing myocardium. From recent studies, it appears evident that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a central role in the arrhythmogenic processes in heart failure by sensing intracellular Ca(2+) 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 (Ca(2+)/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 Ca(2+)/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.
authors.affiliation: Department of Pediatrics, Sanggye Paik Hospital, College of Medicine, Inje University, Seoul, Korea.
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Song
keywords: Arrhythmias cardiac; Calcium-calmodulin-dependent protein kinase type 2; Heart failure; Oxidative stress