| http://purl.uniprot.org/citations/24758151 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24758151 | http://www.w3.org/2000/01/rdf-schema#comment | "CASQ2 (cardiac calsequestrin) is commonly believed to serve as the SR (sarcoplasmic reticulum) luminal Ca2+ sensor. Ablation of CASQ2 promotes SCWs (spontaneous Ca2+ waves) and CPVT (catecholaminergic polymorphic ventricular tachycardia) upon stress but not at rest. How SCWs and CPVT are triggered by stress in the absence of the CASQ2-based luminal Ca2+ sensor is an important unresolved question. In the present study, we assessed the role of the newly identified RyR2 (ryanodine receptor 2)-resident luminal Ca2+ sensor in determining SCW propensity, CPVT susceptibility and cardiac hypertrophy in Casq2-KO (knockout) mice. We crossbred Casq2-KO mice with RyR2 mutant (E4872Q+/-) mice, which lack RyR2-resident SR luminal Ca2+ sensing, to generate animals with both deficiencies. Casq2+/- and Casq2-/-mice showed stress-induced VTs (ventricular tachyarrhythmias), whereas Casq2+/-/E4872Q+/- and Casq2-/-/E4872Q+/-mice displayed little or no stress-induced VTs. Confocal Ca2+ imaging revealed that Casq2-/-hearts frequently exhibited SCWs after extracellular Ca2+ elevation or adrenergic stimulation, whereas Casq2-/-/E4872Q+/-hearts had few or no SCWs under the same conditions. Cardiac hypertrophy developed and CPVT susceptibility increased with age in Casq2-/-mice, but not in Casq2-/-/E4872Q+/-mice. However, the amplitudes and dynamics of voltage-induced Ca2+ transients in Casq2-/- and Casq2-/-/E4872Q+/-hearts were not significantly different. Our results indicate that SCWs, CPVT and hypertrophy in Casq2-null cardiac muscle are governed by the RyR2-resident luminal Ca2+ sensor. This implies that defects in CASQ2-based lumi-nal Ca2+ sensing can be overridden by the RyR2-resident luminal Ca2+ sensor. This makes this RyR2-resident sensor a promising molecular target for the treatment of Ca2+-mediated arrhythmias."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.org/dc/terms/identifier | "doi:10.1042/bj20140126"xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/author | "Chen B."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/author | "Guo A."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/author | "Mi T."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/author | "Wu G."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/author | "Zhou Q."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/author | "Zhong X."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/author | "Chen A.W."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/author | "Song L.S."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/author | "Chen S.R."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/author | "Tan Z."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/author | "Fill M."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/name | "Biochem J"xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/pages | "99-106"xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/title | "The cardiac ryanodine receptor luminal Ca2+ sensor governs Ca2+ waves, ventricular tachyarrhythmias and cardiac hypertrophy in calsequestrin-null mice."xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://purl.uniprot.org/core/volume | "461"xsd:string |
| http://purl.uniprot.org/citations/24758151 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24758151 |
| http://purl.uniprot.org/citations/24758151 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24758151 |
| http://purl.uniprot.org/uniprot/#_A0A1Y7VJP1-mappedCitation-24758151 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24758151 |
| http://purl.uniprot.org/uniprot/#_A0A1Y7VK09-mappedCitation-24758151 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24758151 |
| http://purl.uniprot.org/uniprot/#_F6U7V1-mappedCitation-24758151 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24758151 |