CaMKIIdelta subtypes: localization and function

In this review we discuss the localization and function of the known subtypes of calcium/calmodulin dependent protein kinase II delta (CaMKII delta) and their role in cardiac physiology and pathophysiology. The CaMKII holoenzyme is comprised of multiple subunits that are encoded by four different genes called CaMKII alpha, beta, and gamma. While these four genes have a high degree of sequence homology, they are expressed in different tissues. CaMKII alpha and beta are expressed in neuronal tissue while gamma and delta are present throughout the body, including in the heart. Both CaMKII gamma and delta are alternatively spliced in the heart to generate multiple subtypes. CaMKII delta is the predominant cardiac isoform and is alternatively spliced in the heart to generate the CaMKII delta(B) subtype or the slightly less abundant delta(C) subtype. The CaMKII delta(B) mRNA sequence contains a 33bp insert not present in delta(C) that codes for an 11-amino acid nuclear localization sequence. This review focuses on the localization and function of the CaMKII delta subtypes delta(B) and delta(C) and the role of these subtypes in arrhythmias, contractile dysfunction, gene transcription, and the regulation of Ca2+ handling.