Inhibition of Elevated Ca /Calmodulin-Dependent Protein Kinase II Improves Contractility in Human Failing Myocardium
نویسندگان
چکیده
improved force frequency relationships in the presence of CaMKII inhibitors (KN-93 and AIP). Increased postrest twitches after CaMKII inhibition indicated an improved sarcoplasmic reticulum (SR) Ca loading. This was confirmed in isolated myocytes by a reduced SR Ca spark frequency and hence SR Ca leak, resulting in increased SR Ca load when inhibiting CaMKII. Ryanodine receptor type 2 phosphorylation at Ser2815, which is known to be phosphorylated by CaMKII thereby contributing to SR Ca leak, was found to be
منابع مشابه
Clinical/Translational Research Inhibition of Elevated Ca /Calmodulin-Dependent Protein Kinase II Improves Contractility in Human Failing Myocardium
Rationale: Heart failure (HF) is known to be associated with increased Ca /calmodulin-dependent protein kinase (CaMK)II expression and activity. There is still controversial discussion about the functional role of CaMKII in HF. Moreover, CaMKII inhibition has never been investigated in human myocardium. Objective: We sought to investigate detailed CaMKII expression in end-stage failing human he...
متن کاملInhibition of elevated Ca2+/calmodulin-dependent protein kinase II improves contractility in human failing myocardium.
RATIONALE Heart failure (HF) is known to be associated with increased Ca(2+)/calmodulin-dependent protein kinase (CaMK)II expression and activity. There is still controversial discussion about the functional role of CaMKII in HF. Moreover, CaMKII inhibition has never been investigated in human myocardium. OBJECTIVE We sought to investigate detailed CaMKIIδ expression in end-stage failing huma...
متن کاملCaMKII inhibition in heart failure makes jump to human.
In this issue of Circulation Research, Sossalla et al1 show that acute inhibition of Ca /calmodulin-dependent protein kinase (CaMK)II in failing human myocardium causes functional improvement in contractility by restoring a positive force–frequency relationship (FFR) in cardiac trabeculae. The loss of this normal positive FFR (and often an induction of a negative FFR) is a functional hallmark o...
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Objective(s): The rotavirus nonstructural protein 4 (NSP4) is responsible for the increase in cytoplasmic calcium concentration through a phospholipase C-dependent and phospholipase C-independent pathways in infected cells. It is shown that increasing of intracellular calcium concentration in rotavirus infected cells is associated with the activation of some members of protein kinases family su...
متن کاملCa2+/calmodulin-dependent protein kinase II and protein kinase A differentially regulate sarcoplasmic reticulum Ca2+ leak in human cardiac pathology.
BACKGROUND Sarcoplasmic reticulum (SR) Ca(2+) leak through ryanodine receptor type 2 (RyR2) dysfunction is of major pathophysiological relevance in human heart failure (HF); however, mechanisms underlying progressive RyR2 dysregulation from cardiac hypertrophy to HF are still controversial. METHODS AND RESULTS We investigated healthy control myocardium (n=5) and myocardium from patients with ...
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