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The sarcoplasmic reticulum (SR) Ca²⁺ leak is an important pathomechanism in heart failure (HF). It has been suggested that Ca²⁺/calmodulin‐dependent protein kinase II (CaMKII) is only relevant for the induction of the SR Ca²⁺ leak in non‐ischaemic but not in ischaemic HF. Therefore, we investigated CaMKII and its targets as well as the functional effects of CaMKII inhibition in human ischaemic cardiomyopathy (ICM, n = 37) and dilated cardiomyopathy (DCM, n = 40).

Western blots showed a significantly increased expression (by 54 ± 9%) and autophosphorylation at Thr286 (by 129 ± 29%, P < 0.05 each) of CaMKII in HF compared with healthy myocardium. However, no significant difference could be detected in ICM compared with DCM as to the expression and autophosphorylation of CaMKII nor the phosphorylation of the target sites ryanodine receptor 2 (RyR2)‐S2809 …