Identification and expression of δ-isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human myocardium

Despite its importance for the regulation of heart function, little is known about the isoform expression of the multifunctional Ca2+/calmodulin-dependent protein kinase (CaMKII) in human myocardium. In this study, we investigated the spectrum of CaMKII isoforms delta(2), delta(3), delta(4), delta(8), and delta(9) in human striated muscle tissue. Isoform delta(3) is characteristically expressed in cardiac muscle. In skeletal muscle, specific expression of a new isoform termed delta(11) is demonstrated. Complete sequencing of human delta(2) cDNA, representing all common features of the investigated CaMKII subclass, revealed its high homology to the corresponding rat cDNA. Comparative semiquantitative reverse transcription-polymerase chain reaction analyses from left ventricular tissues of normal hearts and from patients suffering from dilated cardiomyopathy showed a significant increase in transcript levels of isoform delta(3) relative to the expression of glyceraldehyde-3-phosphate dehydrogenase in diseased hearts (101.6+/-11.0% versus 64.9+/-9.9% in the nonfailing group; P<0.05, n = 6). Transcript levels of the other investigated cardiac CaMKII isoforms remained unchanged. At the protein level, by using a subclass-specific antibody, we observed a similar increase of a delta-CaMKII-specific signal (7.2+/-1.0 versus 3.8+/-0.7 optical density units in the nonfailing group; P<0.05, n = 4 through 6). The diseased state of the failing hearts was confirmed by a significant increase in transcript levels for atrial natriuretic peptide (292.9+/-76.4% versus 40.1+/-3.2% in the nonfailing group; P<0.05, n = 3 through 6). Our data characterize for the first time the delta-CaMKII isoform expression pattern in human hearts and demonstrate changes in this expression pattern in heart failure.