| pubmed-article:18347081 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18347081 | lifeskim:mentions | umls-concept:C0006787 | lld:lifeskim |
| pubmed-article:18347081 | lifeskim:mentions | umls-concept:C0233820 | lld:lifeskim |
| pubmed-article:18347081 | lifeskim:mentions | umls-concept:C1419779 | lld:lifeskim |
| pubmed-article:18347081 | lifeskim:mentions | umls-concept:C0596988 | lld:lifeskim |
| pubmed-article:18347081 | lifeskim:mentions | umls-concept:C0596235 | lld:lifeskim |
| pubmed-article:18347081 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:18347081 | lifeskim:mentions | umls-concept:C0205171 | lld:lifeskim |
| pubmed-article:18347081 | lifeskim:mentions | umls-concept:C1999230 | lld:lifeskim |
| pubmed-article:18347081 | lifeskim:mentions | umls-concept:C0699493 | lld:lifeskim |
| pubmed-article:18347081 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:18347081 | pubmed:dateCreated | 2008-4-1 | lld:pubmed |
| pubmed-article:18347081 | pubmed:abstractText | The luminal Ca2+ regulation of cardiac ryanodine receptor (RyR2) was explored at the single channel level. The luminal Ca2+ and Mg2+ sensitivity of single CSQ2-stripped and CSQ2-associated RyR2 channels was defined. Action of wild-type CSQ2 and of two mutant CSQ2s (R33Q and L167H) was also compared. Two luminal Ca2+ regulatory mechanism(s) were identified. One is a RyR2-resident mechanism that is CSQ2 independent and does not distinguish between luminal Ca2+ and Mg2+. This mechanism modulates the maximal efficacy of cytosolic Ca2+ activation. The second luminal Ca2+ regulatory mechanism is CSQ2 dependent and distinguishes between luminal Ca2+ and Mg2+. It does not depend on CSQ2 oligomerization or CSQ2 monomer Ca2+ binding affinity. The key Ca2+-sensitive step in this mechanism may be the Ca2+-dependent CSQ2 interaction with triadin. The CSQ2-dependent mechanism alters the cytosolic Ca2+ sensitivity of the channel. The R33Q CSQ2 mutant can participate in luminal RyR2 Ca2+ regulation but less effectively than wild-type (WT) CSQ2. CSQ2-L167H does not participate in luminal RyR2 Ca2+ regulation. The disparate actions of these two catecholaminergic polymorphic ventricular tachycardia (CPVT)-linked mutants implies that either alteration or elimination of CSQ2-dependent luminal RyR2 regulation can generate the CPVT phenotype. We propose that the RyR2-resident, CSQ2-independent luminal Ca2+ mechanism may assure that all channels respond robustly to large (>5 muM) local cytosolic Ca2+ stimuli, whereas the CSQ2-dependent mechanism may help close RyR2 channels after luminal Ca2+ falls below approximately 0.5 mM. | lld:pubmed |
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| pubmed-article:18347081 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18347081 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18347081 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18347081 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:18347081 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18347081 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:18347081 | pubmed:issn | 1540-7748 | lld:pubmed |
| pubmed-article:18347081 | pubmed:author | pubmed-author:LuoQ AQA | lld:pubmed |
| pubmed-article:18347081 | pubmed:author | pubmed-author:PrioriSilvia... | lld:pubmed |
| pubmed-article:18347081 | pubmed:author | pubmed-author:FillMichaelM | lld:pubmed |
| pubmed-article:18347081 | pubmed:author | pubmed-author:NoriAlessandr... | lld:pubmed |
| pubmed-article:18347081 | pubmed:author | pubmed-author:VolpePompeoP | lld:pubmed |
| pubmed-article:18347081 | pubmed:author | pubmed-author:RizziNicolett... | lld:pubmed |
| pubmed-article:18347081 | pubmed:author | pubmed-author:ValleGiorgiaG | lld:pubmed |
| pubmed-article:18347081 | pubmed:author | pubmed-author:NaniAlmaA | lld:pubmed |
| pubmed-article:18347081 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18347081 | pubmed:volume | 131 | lld:pubmed |
| pubmed-article:18347081 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18347081 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18347081 | pubmed:pagination | 325-34 | lld:pubmed |
| pubmed-article:18347081 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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