Crossing signals: relationships between β-adrenergic stimulation and CaMKII activation

CaMKII is a ubiquitous and pleiotropic serine threonine kinase. The predominant isoform of CaMKII in the heart is CaMKII delta (CaMKIIδ). CaMKII phosphorylates and regulates a number of cardiac proteins involved in excitation-contraction coupling and Ca++ handling including the cardiac ryanodine receptor (RyR2), phospholamban (PLN), the L-type Ca++ channel α1C- and β2a-subunits, and the Na channel (1). Studies using animal models have increasingly linked CaMKII activation and its effects on these targets to the development of heart failure and arrhythmogenesis. There is also considerable evidence that CaMKII expression and activity are increased in human heart failure (1).