title: Calm down when the heart is stressed: Inhibiting calmodulin-dependent protein kinase II for antiarrhythmias.
abstract: Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a pivotal role in many regulatory processes of cellular functions ranging from membrane potentials and electric-contraction (E-C) coupling to mitochondrial integrity and survival of cardiomyocytes. The review article by Hund and Mohler in this issue of Trends in Cardiovascular Medicine highlights the importance of the elevated CaMKII signaling pathways under stressed conditions such as myocardial hypertrophy and ischemia in the detrimental remodeling of ion channels and in the genesis of cardiac arrhythmias. Down-regulation of the elevated CaMKII is now emerging as a powerful therapeutic strategy for the treatment of cardiac arrhythmias and other forms of heart disease such as hypertrophic and ischemic heart failure. The development of new specific and effective CaMKII inhibitors as therapeutic agents for cardiac arrhythmias is challenged by the tremendous complexity of CaMKII expression and distribution of multi isoforms, as well as the multitude of downstream targets in the CaMKII signaling pathways and regulatory processes. A systematic understanding of the structure and regulation of the CaMKII signaling and functional network under the scope of genome and phenome may improve and extend our knowledge about the role of CaMKII in cardiac health and disease and accelerate the discovery of new CaMKII inhibitors that target not only the ATP-binding site but also the regulation sites in the CaMKII signaling and functional network.
authors.affiliation: The Laboratory of Cardiovascular Phenomics, Center for Molecular Medicine, School of Medicine University of Nevada, Reno, NV; Department of Pharmacology, School of Medicine University of Nevada, Reno, NV. Electronic address: dduan@medicine.nevada.edu.
authors.forename: Dayue Darrel
authors.initials: DD
authors.lastname: Duan
mesh_terms: D001145:Arrhythmias, Cardiac / Q000201:enzymology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D006801:Humans
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2