FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2012531906> ?p ?o ?g. }

• W2012531906 endingPage "222" @default.
• W2012531906 startingPage "214" @default.
• W2012531906 abstract "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease characterized by life-threatening arrhythmias elicited by adrenergic activation. CPVT is caused by mutations in the cardiac ryanodine receptor gene (RyR2). In vitro studies demonstrated that RyR2 mutations respond to sympathetic activation with an abnormal diastolic Ca2+ leak from the sarcoplasmic reticulum; however the pathways that mediate the response to adrenergic stimulation have not been defined. In our RyR2R4496C+/− knock-in mouse model of CPVT we tested the hypothesis that inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) counteracts the effects of adrenergic stimulation resulting in an antiarrhythmic activity. CaMKII inhibition with KN-93 completely prevented catecholamine-induced sustained ventricular tachyarrhythmia in RyR2R4496C+/− mice, while the inactive congener KN-92 had no effect. In ventricular myocytes isolated from the hearts of RyR2R4496C+/− mice, CaMKII inhibition with an autocamtide-2 related inhibitory peptide or with KN-93 blunted triggered activity and transient inward currents induced by isoproterenol. Isoproterenol also enhanced the activity of the sarcoplasmic reticulum Ca2+-ATPase (SERCA), increased spontaneous Ca2+ release and spark frequency. CaMKII inhibition blunted each of these parameters without having an effect on the SR Ca2+ content. Our data therefore indicate that CaMKII inhibition is an effective intervention to prevent arrhythmogenesis (both in vivo and in vitro) in the RyR2R4496C+/− knock-in mouse model of CPVT. Mechanistically, CAMKII inhibition acts on several elements of the EC coupling cascade, including an attenuation of SR Ca2+ leak and blunting catecholamine-mediated SERCA activation. CaMKII inhibition may therefore represent a novel therapeutic target for patients with CPVT." @default.
• W2012531906 created "2016-06-24" @default.
• W2012531906 creator A5021196395 @default.
• W2012531906 creator A5028790437 @default.
• W2012531906 creator A5036881486 @default.
• W2012531906 creator A5040092264 @default.
• W2012531906 creator A5064842058 @default.
• W2012531906 creator A5066838003 @default.
• W2012531906 creator A5071398575 @default.
• W2012531906 creator A5083460319 @default.
• W2012531906 creator A5085242419 @default.
• W2012531906 date "2011-01-01" @default.
• W2012531906 modified "2023-09-25" @default.
• W2012531906 title "Calmodulin kinase II inhibition prevents arrhythmias in RyR2R4496C+/− mice with catecholaminergic polymorphic ventricular tachycardia" @default.
• W2012531906 cites W1492161308 @default.
• W2012531906 cites W1521606503 @default.
• W2012531906 cites W1601307541 @default.
• W2012531906 cites W1967365650 @default.
• W2012531906 cites W1986652655 @default.
• W2012531906 cites W1996439106 @default.
• W2012531906 cites W2040505727 @default.
• W2012531906 cites W2052466611 @default.
• W2012531906 cites W2054225000 @default.
• W2012531906 cites W2055917793 @default.
• W2012531906 cites W2055928084 @default.
• W2012531906 cites W2058058175 @default.
• W2012531906 cites W2061051918 @default.
• W2012531906 cites W2064438064 @default.
• W2012531906 cites W2066118117 @default.
• W2012531906 cites W2073472013 @default.
• W2012531906 cites W2081524260 @default.
• W2012531906 cites W2089466188 @default.
• W2012531906 cites W2097102755 @default.
• W2012531906 cites W2097312037 @default.
• W2012531906 cites W2098975719 @default.
• W2012531906 cites W2110333181 @default.
• W2012531906 cites W2118098701 @default.
• W2012531906 cites W2122075276 @default.
• W2012531906 cites W2131133264 @default.
• W2012531906 cites W2139520215 @default.
• W2012531906 cites W2141007146 @default.
• W2012531906 cites W2141823911 @default.
• W2012531906 cites W2149826121 @default.
• W2012531906 cites W2151912878 @default.
• W2012531906 cites W2154620339 @default.
• W2012531906 cites W2159777565 @default.
• W2012531906 cites W2163556700 @default.
• W2012531906 cites W2164327283 @default.
• W2012531906 cites W2166519632 @default.
• W2012531906 cites W2166757867 @default.
• W2012531906 cites W2170620661 @default.
• W2012531906 cites W3021289375 @default.
• W2012531906 doi "https://doi.org/10.1016/j.yjmcc.2010.10.001" @default.
• W2012531906 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20937285" @default.
• W2012531906 hasPublicationYear "2011" @default.
• W2012531906 type Work @default.
• W2012531906 sameAs 2012531906 @default.
• W2012531906 citedByCount "103" @default.
• W2012531906 countsByYear W20125319062012 @default.
• W2012531906 countsByYear W20125319062013 @default.
• W2012531906 countsByYear W20125319062014 @default.
• W2012531906 countsByYear W20125319062015 @default.
• W2012531906 countsByYear W20125319062016 @default.
• W2012531906 countsByYear W20125319062017 @default.
• W2012531906 countsByYear W20125319062018 @default.
• W2012531906 countsByYear W20125319062019 @default.
• W2012531906 countsByYear W20125319062020 @default.
• W2012531906 countsByYear W20125319062021 @default.
• W2012531906 countsByYear W20125319062022 @default.
• W2012531906 countsByYear W20125319062023 @default.
• W2012531906 crossrefType "journal-article" @default.
• W2012531906 hasAuthorship W2012531906A5021196395 @default.
• W2012531906 hasAuthorship W2012531906A5028790437 @default.
• W2012531906 hasAuthorship W2012531906A5036881486 @default.
• W2012531906 hasAuthorship W2012531906A5040092264 @default.
• W2012531906 hasAuthorship W2012531906A5064842058 @default.
• W2012531906 hasAuthorship W2012531906A5066838003 @default.
• W2012531906 hasAuthorship W2012531906A5071398575 @default.
• W2012531906 hasAuthorship W2012531906A5083460319 @default.
• W2012531906 hasAuthorship W2012531906A5085242419 @default.
• W2012531906 hasConcept C113217602 @default.
• W2012531906 hasConcept C126322002 @default.
• W2012531906 hasConcept C134018914 @default.
• W2012531906 hasConcept C158617107 @default.
• W2012531906 hasConcept C170493617 @default.
• W2012531906 hasConcept C181199279 @default.
• W2012531906 hasConcept C185592680 @default.
• W2012531906 hasConcept C190712762 @default.
• W2012531906 hasConcept C23265538 @default.
• W2012531906 hasConcept C2775894120 @default.
• W2012531906 hasConcept C2776824294 @default.
• W2012531906 hasConcept C2778178275 @default.
• W2012531906 hasConcept C2781414619 @default.
• W2012531906 hasConcept C29688787 @default.
• W2012531906 hasConcept C519063684 @default.
• W2012531906 hasConcept C55493867 @default.
• W2012531906 hasConcept C71924100 @default.
• W2012531906 hasConcept C86803240 @default.

• next