| pubmed-article:17052727 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17052727 | lifeskim:mentions | umls-concept:C0036226 | lld:lifeskim |
| pubmed-article:17052727 | lifeskim:mentions | umls-concept:C0248868 | lld:lifeskim |
| pubmed-article:17052727 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:17052727 | lifeskim:mentions | umls-concept:C0035028 | lld:lifeskim |
| pubmed-article:17052727 | lifeskim:mentions | umls-concept:C0000894 | lld:lifeskim |
| pubmed-article:17052727 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:17052727 | lifeskim:mentions | umls-concept:C0599894 | lld:lifeskim |
| pubmed-article:17052727 | lifeskim:mentions | umls-concept:C0596235 | lld:lifeskim |
| pubmed-article:17052727 | lifeskim:mentions | umls-concept:C0234112 | lld:lifeskim |
| pubmed-article:17052727 | lifeskim:mentions | umls-concept:C0521116 | lld:lifeskim |
| pubmed-article:17052727 | lifeskim:mentions | umls-concept:C1521840 | lld:lifeskim |
| pubmed-article:17052727 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:17052727 | pubmed:dateCreated | 2006-12-25 | lld:pubmed |
| pubmed-article:17052727 | pubmed:abstractText | Cardiac Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in heart has been implicated in Ca(2+) current (I(Ca)) facilitation, enhanced sarcoplasmic reticulum (SR) Ca(2+) release and frequency-dependent acceleration of relaxation (FDAR) via enhanced SR Ca(2+) uptake. However, questions remain about how CaMKII may work in these three processes. Here we tested the role of CaMKII in these processes using transgenic mice (SR-AIP) that express four concatenated repeats of the CaMKII inhibitory peptide AIP selectively in the SR membrane. Wild type mice (WT) and mice expressing AIP exclusively in the nucleus (NLS-AIP) served as controls. Increasing stimulation frequency produced typical FDAR in WT and NLS-AIP, but FDAR was markedly inhibited in SR-AIP. Quantitative analysis of cytosolic Ca(2+) removal during [Ca(2+)](i) decline revealed that FDAR is due to an increased apparent V(max) of SERCA. CaMKII-dependent RyR phosphorylation at Ser2815 and SR Ca(2+) leak was both decreased in SR-AIP vs. WT. This decrease in SR Ca(2+) leak may partly balance the reduced SERCA activity leading to relatively unaltered SR-Ca(2+) load in SR-AIP vs. WT myocytes. Surprisingly, CaMKII regulation of the L-type Ca(2+) channel (I(Ca) facilitation and recovery from inactivation) was abolished by the SR-targeted CaMKII inhibition in SR-AIP mice. Inhibition of CaMKII effects on I(Ca) and RyR function by the SR-localized AIP places physical constraints on the localization of these proteins at the junctional microdomain. Thus SR-targeted CaMKII inhibition can directly inhibit the activation of SR Ca(2+) uptake, SR Ca(2+) release and I(Ca) by CaMKII, effects which have all been implicated in triggered arrhythmias. | lld:pubmed |
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| pubmed-article:17052727 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17052727 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17052727 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:17052727 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17052727 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:17052727 | pubmed:issn | 0022-2828 | lld:pubmed |
| pubmed-article:17052727 | pubmed:author | pubmed-author:BersDonald... | lld:pubmed |
| pubmed-article:17052727 | pubmed:author | pubmed-author:KaetzelMarcia... | lld:pubmed |
| pubmed-article:17052727 | pubmed:author | pubmed-author:DedmanJohn... | lld:pubmed |
| pubmed-article:17052727 | pubmed:author | pubmed-author:HukeSabineS | lld:pubmed |
| pubmed-article:17052727 | pubmed:author | pubmed-author:DeSantiagoJai... | lld:pubmed |
| pubmed-article:17052727 | pubmed:author | pubmed-author:PichtEckardE | lld:pubmed |
| pubmed-article:17052727 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17052727 | pubmed:volume | 42 | lld:pubmed |
| pubmed-article:17052727 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17052727 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17052727 | pubmed:pagination | 196-205 | lld:pubmed |
| pubmed-article:17052727 | pubmed:dateRevised | 2010-12-3 | lld:pubmed |
| pubmed-article:17052727 | pubmed:meshHeading | pubmed-meshheading:17052727... | lld:pubmed |
| pubmed-article:17052727 | pubmed:meshHeading | pubmed-meshheading:17052727... | lld:pubmed |
| pubmed-article:17052727 | pubmed:meshHeading | pubmed-meshheading:17052727... | lld:pubmed |
| pubmed-article:17052727 | pubmed:meshHeading | pubmed-meshheading:17052727... | lld:pubmed |
