Camkii Delta Splice Variants In The Healthy And Diseased Heart

RNA splicing has been recognized in recent years as a pivotal player in heart development and disease. The Ca2+/calmodulin dependent protein kinase II delta (CaMKII delta) is a multifunctional Ser/Thr kinase family and generates at least 11 different splice variants through alternative splicing. This enzyme, which belongs to the CaMKII family, is the predominant family member in the heart and functions as a messenger toward adaptive or detrimental signaling in cardiomyocytes. Classically, the nuclear CaMKII delta B and cytoplasmic CaMKII delta C splice variants are described as mediators of arrhythmias, contractile function, Ca2+ handling, and gene transcription. Recent findings also put CaMKII delta A and CaMKII delta 9 as cardinal players in the global CaMKII response in the heart. In this review, we discuss and summarize the new insights into CaMKII delta splice variants and their (proposed) functions, as well as CaMKII-engineered mouse phenotypes and cardiac dysfunction related to CaMKII delta missplicing. We also discuss RNA splicing factors affecting CaMKII splicing. Finally, we discuss the translational perspective derived from these insights and future directions on CaMKII delta splicing research in the healthy and diseased heart.