File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Arrhythmia and sudden death associated with elevated cardiac chloride channel activity

TitleArrhythmia and sudden death associated with elevated cardiac chloride channel activity
Authors
Issue Date2011
PublisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1582-1838
Citation
Journal Of Cellular And Molecular Medicine, 2011, v. 15 n. 11, p. 2307-2316 How to Cite?
AbstractThe identification and analysis of several cationic ion channels and their associated genes have greatly improved our understanding of the molecular and cellular mechanisms of cardiac arrhythmia. Our objective in this study was to examine the involvement of anionic ion channels in cardiac arrhythmia. We used a transgenic mouse model to overexpress the human cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a cAMP-regulated chloride channel. We used RNase protection and in situ hybridization assays to determine the level of CFTR expression, and radiotelemetry and in vivo electrophysiological study in combination with pharmacological intervention to analyse the cardiac function. Cardiac CFTR overexpression leads to stress-related sudden death in this model. In vivo intracardiac electrophysiological studies performed in anaesthetized mice showed no significant differences in baseline conduction parameters including atrial-His bundle (AH) or His bundle-ventricular (HV) conduction intervals, atrioventricular (AV) Wenckebach or 2:1 AV block cycle length and AV nodal functional refractory period. However, following isoproterenol administration, there was marked slowing of conduction parameters, including high-grade AV block in transgenic mice, with non-sustained ventricular tachycardia easily inducible using programmed stimulation or burst pacing. Our sudden death mouse model can be a valuable tool for investigation of the role of chloride channels in arrhythmogenesis and, potentially, for future evaluation of novel anti-arrhythmic therapeutic strategies and pharmacological agents. © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/178245
ISSN
2012 Impact Factor: 4.753
2015 SCImago Journal Rankings: 1.941
References

 

DC FieldValueLanguage
dc.contributor.authorYe, Len_US
dc.contributor.authorZhu, Wen_US
dc.contributor.authorBackx, PHen_US
dc.contributor.authorCortez, MAen_US
dc.contributor.authorWu, Jen_US
dc.contributor.authorChow, YHen_US
dc.contributor.authorMckerlie, Cen_US
dc.contributor.authorWang, Aen_US
dc.contributor.authorTsui, LCen_US
dc.contributor.authorGross, GJen_US
dc.contributor.authorHu, Jen_US
dc.date.accessioned2012-12-19T09:43:52Z-
dc.date.available2012-12-19T09:43:52Z-
dc.date.issued2011en_US
dc.identifier.citationJournal Of Cellular And Molecular Medicine, 2011, v. 15 n. 11, p. 2307-2316en_US
dc.identifier.issn1582-1838en_US
dc.identifier.urihttp://hdl.handle.net/10722/178245-
dc.description.abstractThe identification and analysis of several cationic ion channels and their associated genes have greatly improved our understanding of the molecular and cellular mechanisms of cardiac arrhythmia. Our objective in this study was to examine the involvement of anionic ion channels in cardiac arrhythmia. We used a transgenic mouse model to overexpress the human cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a cAMP-regulated chloride channel. We used RNase protection and in situ hybridization assays to determine the level of CFTR expression, and radiotelemetry and in vivo electrophysiological study in combination with pharmacological intervention to analyse the cardiac function. Cardiac CFTR overexpression leads to stress-related sudden death in this model. In vivo intracardiac electrophysiological studies performed in anaesthetized mice showed no significant differences in baseline conduction parameters including atrial-His bundle (AH) or His bundle-ventricular (HV) conduction intervals, atrioventricular (AV) Wenckebach or 2:1 AV block cycle length and AV nodal functional refractory period. However, following isoproterenol administration, there was marked slowing of conduction parameters, including high-grade AV block in transgenic mice, with non-sustained ventricular tachycardia easily inducible using programmed stimulation or burst pacing. Our sudden death mouse model can be a valuable tool for investigation of the role of chloride channels in arrhythmogenesis and, potentially, for future evaluation of novel anti-arrhythmic therapeutic strategies and pharmacological agents. © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.en_US
dc.languageengen_US
dc.publisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1582-1838en_US
dc.relation.ispartofJournal of Cellular and Molecular Medicineen_US
dc.subject.meshAnimalsen_US
dc.subject.meshArrhythmias, Cardiac - Chemically Induced - Metabolismen_US
dc.subject.meshAtrioventricular Block - Chemically Induceden_US
dc.subject.meshAtrioventricular Node - Physiopathologyen_US
dc.subject.meshBradycardia - Chemically Induceden_US
dc.subject.meshCardiac Pacing, Artificialen_US
dc.subject.meshChloride Channels - Metabolismen_US
dc.subject.meshCystic Fibrosis Transmembrane Conductance Regulator - Biosynthesis - Genetics - Metabolismen_US
dc.subject.meshDeath, Sudden, Cardiacen_US
dc.subject.meshHearten_US
dc.subject.meshHeart Conduction System - Physiopathologyen_US
dc.subject.meshIn Situ Hybridizationen_US
dc.subject.meshIsoproterenol - Administration & Dosage - Pharmacologyen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred C57blen_US
dc.subject.meshMice, Transgenicen_US
dc.subject.meshMyocardium - Metabolismen_US
dc.subject.meshTachycardia, Ventricularen_US
dc.titleArrhythmia and sudden death associated with elevated cardiac chloride channel activityen_US
dc.typeArticleen_US
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_US
dc.identifier.authorityTsui, LC=rp00058en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1582-4934.2010.01243.xen_US
dc.identifier.pmid21155978-
dc.identifier.scopuseid_2-s2.0-80054914585en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80054914585&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume15en_US
dc.identifier.issue11en_US
dc.identifier.spage2307en_US
dc.identifier.epage2316en_US
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridYe, L=35504324300en_US
dc.identifier.scopusauthoridZhu, W=7404232380en_US
dc.identifier.scopusauthoridBackx, PH=7006796226en_US
dc.identifier.scopusauthoridCortez, MA=7005014445en_US
dc.identifier.scopusauthoridWu, J=53878800700en_US
dc.identifier.scopusauthoridChow, YH=7202906132en_US
dc.identifier.scopusauthoridMckerlie, C=35993902900en_US
dc.identifier.scopusauthoridWang, A=7404620105en_US
dc.identifier.scopusauthoridTsui, LC=7102754167en_US
dc.identifier.scopusauthoridGross, GJ=7403208464en_US
dc.identifier.scopusauthoridHu, J=7406420553en_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats