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http://purl.uniprot.org/citations/21252154http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21252154http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

In heart failure Ca/calmodulin kinase (CaMK)II expression and reactive oxygen species (ROS) are increased. Both ROS and CaMKII can increase late I(Na) leading to intracellular Na accumulation and arrhythmias. It has been shown that ROS can activate CaMKII via oxidation.

Objective

We tested whether CaMKIIδ is required for ROS-dependent late I(Na) regulation and whether ROS-induced Ca released from the sarcoplasmic reticulum (SR) is involved.

Methods and results

40 μmol/L H(2)O(2) significantly increased CaMKII oxidation and autophosphorylation in permeabilized rabbit cardiomyocytes. Without free [Ca](i) (5 mmol/L BAPTA/1 mmol/L Br(2)-BAPTA) or after SR depletion (caffeine 10 mmol/L, thapsigargin 5 μmol/L), the H(2)O(2)-dependent CaMKII oxidation and autophosphorylation was abolished. H(2)O(2) significantly increased SR Ca spark frequency (confocal microscopy) but reduced SR Ca load. In wild-type (WT) mouse myocytes, H(2)O(2) increased late I(Na) (whole cell patch-clamp). This increase was abolished in CaMKIIδ(-/-) myocytes. H(2)O(2)-induced [Na](i) and [Ca](i) accumulation (SBFI [sodium-binding benzofuran isophthalate] and Indo-1 epifluorescence) was significantly slowed in CaMKIIδ(-/-) myocytes (versus WT). CaMKIIδ(-/-) myocytes developed significantly less H(2)O(2)-induced arrhythmias and were more resistant to hypercontracture. Opposite results (increased late I(Na), [Na](i) and [Ca](i) accumulation) were obtained by overexpression of CaMKIIδ in rabbit myocytes (adenoviral gene transfer) reversible with CaMKII inhibition (10 μmol/L KN93 or 0.1 μmol/L AIP [autocamtide 2-related inhibitory peptide]).

Conclusions

Free [Ca](i) and a functional SR are required for ROS activation of CaMKII. ROS-activated CaMKIIδ enhances late I(Na), which may lead to cellular Na and Ca overload. This may be of relevance in hear failure, where enhanced ROS production meets increased CaMKII expression."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.org/dc/terms/identifier"doi:10.1161/circresaha.110.221911"xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/author"Wagner S."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/author"Backs J."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/author"Anderson M.E."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/author"Schulte T."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/author"Bers D.M."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/author"Grandi E."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/author"Maier L.S."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/author"Sowa T."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/author"Belardinelli L."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/author"Weber S.L."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/author"Bellmann S."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/author"Ruff H.M."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/name"Circ Res"xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/pages"555-565"xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/title"Reactive oxygen species-activated Ca/calmodulin kinase IIdelta is required for late I(Na) augmentation leading to cellular Na and Ca overload."xsd:string
http://purl.uniprot.org/citations/21252154http://purl.uniprot.org/core/volume"108"xsd:string
http://purl.uniprot.org/citations/21252154http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21252154
http://purl.uniprot.org/citations/21252154http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21252154
http://purl.uniprot.org/uniprot/#_D3Z7K9-mappedCitation-21252154http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21252154
http://purl.uniprot.org/uniprot/#_A0A0G2JGS4-mappedCitation-21252154http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21252154
http://purl.uniprot.org/uniprot/#_E9QAJ4-mappedCitation-21252154http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21252154
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