Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/18419777http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18419777http://www.w3.org/2000/01/rdf-schema#comment"

Aim

To explore the physiological consequences of the ryanodine receptor (RyR2)-P2328S mutation associated with catecholaminergic polymorphic ventricular tachycardia (CPVT).

Methods

We generated heterozygotic (RyR2 p/s) and homozygotic (RyR2 s/s) transgenic mice and studied Ca2+ signals from regularly stimulated, Fluo-3-loaded, cardiac myocytes. Results were compared with monophasic action potentials (MAPs) in Langendorff-perfused hearts under both regular and programmed electrical stimulation (PES).

Results

Evoked Ca2+ transients from wild-type (WT), heterozygote (RyR2 p/s) and homozygote (RyR2 s/s) myocytes had indistinguishable peak amplitudes with RyR2 s/s showing subsidiary events. Adding 100 nm isoproterenol produced both ectopic peaks and subsidiary events in WT but not RyR2 p/s and ectopic peaks and reduced amplitudes of evoked peaks in RyR2 s/s. Regularly stimulated WT, RyR2 p/s and RyR2 s/s hearts showed indistinguishable MAP durations and refractory periods. RyR2 p/s hearts showed non-sustained ventricular tachycardias (nsVTs) only with PES. Both nsVTs and sustained VTs (sVTs) occurred with regular stimuli and PES with isoproterenol treatment. RyR2 s/s hearts showed higher incidences of nsVTs before but mainly sVTs after introduction of isoproterenol with both regular stimuli and PES, particularly at higher pacing frequencies. Additionally, intrinsically beating RyR2 s/s showed extrasystolic events often followed by spontaneous sVT.

Conclusion

The RyR2-P2328S mutation results in marked alterations in cellular Ca2+ homeostasis and arrhythmogenic properties resembling CPVT with greater effects in the homozygote than the heterozygote demonstrating an important gene dosage effect."xsd:string
http://purl.uniprot.org/citations/18419777http://purl.org/dc/terms/identifier"doi:10.1111/j.1748-1716.2008.01865.x"xsd:string
http://purl.uniprot.org/citations/18419777http://purl.uniprot.org/core/author"Zhang Y."xsd:string
http://purl.uniprot.org/citations/18419777http://purl.uniprot.org/core/author"Colledge W.H."xsd:string
http://purl.uniprot.org/citations/18419777http://purl.uniprot.org/core/author"Williams A.J."xsd:string
http://purl.uniprot.org/citations/18419777http://purl.uniprot.org/core/author"Huang C.L."xsd:string
http://purl.uniprot.org/citations/18419777http://purl.uniprot.org/core/author"Grace A.A."xsd:string
http://purl.uniprot.org/citations/18419777http://purl.uniprot.org/core/author"Goddard C.A."xsd:string
http://purl.uniprot.org/citations/18419777http://purl.uniprot.org/core/author"Ghais N.S."xsd:string
http://purl.uniprot.org/citations/18419777http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18419777http://purl.uniprot.org/core/name"Acta Physiol (Oxf)"xsd:string
http://purl.uniprot.org/citations/18419777http://purl.uniprot.org/core/pages"123-140"xsd:string
http://purl.uniprot.org/citations/18419777http://purl.uniprot.org/core/title"Physiological consequences of the P2328S mutation in the ryanodine receptor (RyR2) gene in genetically modified murine hearts."xsd:string
http://purl.uniprot.org/citations/18419777http://purl.uniprot.org/core/volume"194"xsd:string
http://purl.uniprot.org/citations/18419777http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18419777
http://purl.uniprot.org/citations/18419777http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18419777
http://purl.uniprot.org/uniprot/#_A0A1Y7VJP1-mappedCitation-18419777http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18419777
http://purl.uniprot.org/uniprot/#_A0A1Y7VK09-mappedCitation-18419777http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18419777
http://purl.uniprot.org/uniprot/#_F6U7V1-mappedCitation-18419777http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18419777
http://purl.uniprot.org/uniprot/#_E9Q401-mappedCitation-18419777http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18419777
http://purl.uniprot.org/uniprot/#_Q60835-mappedCitation-18419777http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18419777
http://purl.uniprot.org/uniprot/#_Q80ZZ5-mappedCitation-18419777http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18419777
http://purl.uniprot.org/uniprot/#_Q9CTT8-mappedCitation-18419777http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18419777
http://purl.uniprot.org/uniprot/F6U7V1http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/18419777
▶