Identification and expression of delta-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 know n about the isoform expression of the multifunctional Ca2+/calmodulin-depen dent protein kinase (CaMKII) in human myocardium. In this study, we investi gated 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 charac teristically expressed in cardiac muscle. In skeletal muscle, specific expr ession of a new isoform termed delta(11) is demonstrated. Complete sequenci ng of human delta(2) cDNA, representing all common features of the investig ated CaMKII subclass, revealed its high homology to the corresponding rat c DNA. Comparative semiquantitative reverse transcription-polymerase chain re action analyses from left ventricular tissues of normal hearts and from pat ients suffering from dilated cardiomyopathy showed a significant increase i n transcript levels of isoform delta(3) relative to the expression of glyce raldehyde-3-phosphate dehydrogenase in diseased hearts (101.6+/-11.0% versu s 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 opt ical density units in the nonfailing group; P<0.05, n = 4 through 6). The d iseased 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 cha racterize for the first time the delta-CaMKII isoform expression pattern in human hearts and demonstrate changes in this expression pattern in heart f ailure.