Ryanodine receptor (RyR2) dysfunction, which may result from a variety of 
mechanisms, has been implicated in the pathogenesis of cardiac arrhythmias and 
heart failure. In this review, we discuss the important role of 
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in the regulation of 
RyR2-mediated Ca(2+) release. In particular, we examine how pathological 
activation of CaMKII can lead to an increased risk of sudden arrhythmic death. 
Finally, we discuss how reduction of CaMKII-mediated RyR2 hyperactivity might 
reduce the risk of arrhythmias and may serve as a rationale for future 
pharmacotherapeutic approaches.