Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/20944434http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20944434http://www.w3.org/2000/01/rdf-schema#comment"

Background

Dantrolene, a specific agent for the treatment of malignant hyperthermia, was found to inhibit Ca(2+) leak through not only the skeletal ryanodine receptor (RyR1), but also the cardiac ryanodine receptor (RyR2) by correcting the defective inter-domain interaction between N-terminal (1-619 amino acid) and central (2,000-2,500 amino acid) domains of RyRs. Here, the in vivo anti-arrhythmic effect of dantrolene in a human catecholaminergic polymorphic ventricular tachycardia (CPVT)-associated RyR2(R2474S/+) knock-in (KI) mouse model was investigated.

Methods and results

ECG was monitored in KI mice (n=6) and wild-type (WT) mice (n=6), before and after an injection of epinephrine (1.0mg/kg) or on exercise using a treadmill. In all KI (but not WT) mice, bi-directional ventricular tachycardia (VT) was induced after an injection of epinephrine or on exercise. Pre-treatment with dantrolene (for 7-10 days) significantly inhibited the inducible VT (P<0.01). In KI cardiomyocytes, Ca(2+) spark frequency (SpF; s(-1)·100µm(-1): 5.8±0.3, P<0.01) was much more increased after the addition of isoproterenol than in WT cardiomyocytes (SpF: 3.6±0.2). The increase in SpF seen in KI cardiomyocytes was attenuated by 1.0µmol/L dantrolene (SpF: 3.6±0.5, P<0.01).

Conclusions

Dantrolene prevents CPVT, presumably by inhibiting Ca(2+) leak through the RyR2."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.org/dc/terms/identifier"doi:10.1253/circj.cj-10-0680"xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Oda T."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Matsuzaki M."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Kobayashi S."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Yamamoto T."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Xu X."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Yano M."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Ono M."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Doi M."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Okuda S."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Susa T."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Tateishi H."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Suetomi T."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/author"Uchinoumi H."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/name"Circ J"xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/pages"2579-2584"xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/title"Dantrolene, a therapeutic agent for malignant hyperthermia, inhibits catecholaminergic polymorphic ventricular tachycardia in a RyR2(R2474S/+) knock-in mouse model."xsd:string
http://purl.uniprot.org/citations/20944434http://purl.uniprot.org/core/volume"74"xsd:string
http://purl.uniprot.org/citations/20944434http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20944434
http://purl.uniprot.org/citations/20944434http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20944434
http://purl.uniprot.org/uniprot/#_E9Q401-mappedCitation-20944434http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20944434
http://purl.uniprot.org/uniprot/#_Q60835-mappedCitation-20944434http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20944434
▶