| pubmed-article:18007024 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18007024 | lifeskim:mentions | umls-concept:C0026809 | lld:lifeskim |
| pubmed-article:18007024 | lifeskim:mentions | umls-concept:C2339371 | lld:lifeskim |
| pubmed-article:18007024 | lifeskim:mentions | umls-concept:C0031715 | lld:lifeskim |
| pubmed-article:18007024 | lifeskim:mentions | umls-concept:C0521390 | lld:lifeskim |
| pubmed-article:18007024 | lifeskim:mentions | umls-concept:C0070876 | lld:lifeskim |
| pubmed-article:18007024 | lifeskim:mentions | umls-concept:C0221099 | lld:lifeskim |
| pubmed-article:18007024 | lifeskim:mentions | umls-concept:C0332281 | lld:lifeskim |
| pubmed-article:18007024 | lifeskim:mentions | umls-concept:C0035028 | lld:lifeskim |
| pubmed-article:18007024 | lifeskim:mentions | umls-concept:C0392756 | lld:lifeskim |
| pubmed-article:18007024 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:18007024 | pubmed:dateCreated | 2008-2-1 | lld:pubmed |
| pubmed-article:18007024 | pubmed:abstractText | Stimulation of nitric oxide (NO) release from the coronary endothelium facilitates myocardial relaxation via a cGMP-dependent reduction in myofilament Ca2+ sensitivity. Recent evidence suggests that NO released by a neuronal NO synthase (nNOS) in the myocardium can also hasten left ventricular relaxation; however, the mechanism underlying these findings is uncertain. Here we show that both relaxation (TR50) and the rate of [Ca2+]i transient decay (tau) are significantly prolonged in field-stimulated or voltage-clamped left ventricular myocytes from nNOS-/- mice and in wild-type myocytes (nNOS+/+) after acute nNOS inhibition. Disabling the sarcoplasmic reticulum abolished the differences in TR50 and tau, suggesting that impaired sarcoplasmic reticulum Ca2+ reuptake may account for the slower relaxation in nNOS-/- mice. In line with these findings, disruption of nNOS (but not of endothelial NOS) decreased phospholamban phosphorylation (P-Ser16 PLN), whereas nNOS inhibition had no effect on TR50 or tau in PLN-/- myocytes. Inhibition of cGMP signaling had no effect on relaxation in either group whereas protein kinase A inhibition abolished the difference in relaxation and PLN phosphorylation by decreasing P-Ser16 PLN and prolonging TR50 in nNOS+/+ myocytes. Conversely, inhibition of type 1 or 2A protein phosphatases shortened TR50 and increased P-Ser16 PLN in nNOS-/- but not in nNOS+/+ myocytes, in agreement with data showing increased protein phosphatase activity in nNOS-/- hearts. Taken together, our findings identify a novel mechanism by which myocardial nNOS promotes left ventricular relaxation by regulating the protein kinase A-mediated phosphorylation of PLN and the rate of sarcoplasmic reticulum Ca2+ reuptake via a cGMP-independent effect on protein phosphatase activity. | lld:pubmed |
| pubmed-article:18007024 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18007024 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18007024 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18007024 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18007024 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18007024 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18007024 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18007024 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18007024 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18007024 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18007024 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18007024 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:18007024 | pubmed:issn | 1524-4571 | lld:pubmed |
| pubmed-article:18007024 | pubmed:author | pubmed-author:El-ArmoucheAl... | lld:pubmed |
| pubmed-article:18007024 | pubmed:author | pubmed-author:KraniasEvange... | lld:pubmed |
| pubmed-article:18007024 | pubmed:author | pubmed-author:RedwoodCharle... | lld:pubmed |
| pubmed-article:18007024 | pubmed:author | pubmed-author:CasadeiBarbar... | lld:pubmed |
| pubmed-article:18007024 | pubmed:author | pubmed-author:SearsClaire... | lld:pubmed |
| pubmed-article:18007024 | pubmed:author | pubmed-author:ZhangYin... | lld:pubmed |
| pubmed-article:18007024 | pubmed:author | pubmed-author:EmanuelKrzysz... | lld:pubmed |
| pubmed-article:18007024 | pubmed:author | pubmed-author:ZhangMei... | lld:pubmed |
| pubmed-article:18007024 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18007024 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:18007024 | pubmed:volume | 102 | lld:pubmed |
| pubmed-article:18007024 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18007024 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18007024 | pubmed:pagination | 242-9 | lld:pubmed |
| pubmed-article:18007024 | pubmed:meshHeading | pubmed-meshheading:18007024... | lld:pubmed |
| pubmed-article:18007024 | pubmed:meshHeading | pubmed-meshheading:18007024... | lld:pubmed |
| pubmed-article:18007024 | pubmed:meshHeading | pubmed-meshheading:18007024... | lld:pubmed |
| pubmed-article:18007024 | pubmed:meshHeading | pubmed-meshheading:18007024... | lld:pubmed |
| pubmed-article:18007024 | pubmed:meshHeading | pubmed-meshheading:18007024... | lld:pubmed |
| pubmed-article:18007024 | pubmed:meshHeading | pubmed-meshheading:18007024... | lld:pubmed |
| pubmed-article:18007024 | pubmed:meshHeading | pubmed-meshheading:18007024... | lld:pubmed |
| pubmed-article:18007024 | pubmed:meshHeading | pubmed-meshheading:18007024... | lld:pubmed |
| pubmed-article:18007024 | pubmed:meshHeading | pubmed-meshheading:18007024... | lld:pubmed |
| pubmed-article:18007024 | pubmed:meshHeading | pubmed-meshheading:18007024... | lld:pubmed |
| pubmed-article:18007024 | pubmed:meshHeading | pubmed-meshheading:18007024... | lld:pubmed |
| pubmed-article:18007024 | pubmed:meshHeading | pubmed-meshheading:18007024... | lld:pubmed |
| pubmed-article:18007024 | pubmed:year | 2008 | lld:pubmed |
| pubmed-article:18007024 | pubmed:articleTitle | Reduced phospholamban phosphorylation is associated with impaired relaxation in left ventricular myocytes from neuronal NO synthase-deficient mice. | lld:pubmed |
| pubmed-article:18007024 | pubmed:affiliation | Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom. | lld:pubmed |
| pubmed-article:18007024 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:18007024 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:18125 | entrezgene:pubmed | pubmed-article:18007024 | lld:entrezgene |
| entrez-gene:18127 | entrezgene:pubmed | pubmed-article:18007024 | lld:entrezgene |
| entrez-gene:18821 | entrezgene:pubmed | pubmed-article:18007024 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:18007024 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:18007024 | lld:entrezgene |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18007024 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18007024 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18007024 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18007024 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18007024 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18007024 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18007024 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18007024 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18007024 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18007024 | lld:pubmed |
