Calcium/
calmodulin (Ca(2+)/CaM) dependent
protein kinase II (
CaMKII) has emerged as a key
nodal protein in the regulation of cardiac physiology and pathology. Due to the particularly elegant relationship between the structure and function of the
kinase,
CaMKII is able to translate a diverse set of signaling events into downstream physiological effects. While
CaMKII is typically autoinhibited at basal conditions, prolonged rapid Ca(2+) cycling can activate the
kinase and allow post-translational modifications that depend critically on the biochemical environment of the heart. These modifications result in sustained, autonomous
CaMKII activation and have been associated with pathological cardiac signaling. Indeed, improved understanding of
CaMKII activation mechanisms could potentially lead to new clinical
therapies for the treatment or prevention of
cardiovascular disease. Here we review the known mechanisms of
CaMKII activation and discuss some of the pathological signaling pathways in which they play a role.