CaMKII comes of age in cardiac health and disease

Almost four decades since its initial discovery in brain (Schulman and Greengard, 1978), the multifunctional Ca 2+ and calmodulindependent protein kinase II (CaMKII) has now emerged as a key signaling molecule in the heart.The isoform that predominates in heart, CaMKIIδ, directly regulates expression and function of several of the main cardiac ion channels and Ca 2+ handling proteins (Bers and Grandi, 2009).CaMKII-dependent effects are thought to orchestrate many of the electrophysiologic and contractile adaptations to common cardiac stressors, such as rapid pacing, adrenergic stimulation, and oxidative challenge.In the context of disease, CaMKII has been shown to contribute to a remarkably wide variety of cardiac pathologies, including myocardial hypertrophy, ischemia, heart failure (HF), and arrhythmia.CaMKII expression is increased in patients with HF (Hoch et al., 1999), and elevated CaMKII expression and activity have been implicated in the transition to HF (Zhang et al., 2003).Indeed, inhibiting CaMKII appears to reduce arrhythmias and pathological signaling, which makes this kinase a promising new therapeutic target (Anderson et al., 2011).