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dc.contributor.authorValli, Haseeben
dc.contributor.authorAhmad, Shirazen
dc.contributor.authorJiang, Anita Yen
dc.contributor.authorSmyth, Roberten
dc.contributor.authorJeevaratnam, Kamalanen
dc.contributor.authorMatthews, Hughen
dc.contributor.authorHuang, Christopheren
dc.date.accessioned2018-02-12T17:52:08Z
dc.date.available2018-02-12T17:52:08Z
dc.date.issued2018-01en
dc.identifier.issn0047-6374
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/273166
dc.description.abstractIntroduction Recent studies reported that energetically deficient murine Pgc-1β-/- hearts replicate age-dependent atrial arrhythmic phenotypes associated with their corresponding clinical conditions, implicating action potential (AP) conduction slowing consequent upon reduced AP upstroke rates. Materials and Methods. We tested a hypothesis implicating Na+ current alterations as a mechanism underlying these electrophysiological phenotypes. We applied loose patch-clamp techniques to intact young and aged, WT and Pgc-1β-/-, atrial cardiomyocyte preparations preserving their in vivo extracellular and intracellular conditions. Results and Discussion Depolarising steps activated typical voltage-dependent activating and inactivating inward (Na+) currents whose amplitude increased or decreased with the amplitudes of the activating, or preceding inactivating, steps. Maximum values of peak Na+ current were independently influenced by genotype but not age or interacting effects of genotype and age on two-way ANOVA. Neither genotype, nor age, whether independently or interactively, influenced voltages at half-maximal current, or steepness factors, for current activation and inactivation, or time constants for recovery from inactivation following repolarisation. In contrast, delayed outward (K+) currents showed similar activation and rectification properties through all experimental groups. These findings directly demonstrate and implicate reduced Na+ in contrast to unchanged K+ current, as a mechanism for slowed conduction causing atrial arrhythmogenicity in Pgc-1β-/- hearts.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherElsevier
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectHeart Atriaen
dc.subjectMyocytes, Cardiacen
dc.subjectAnimalsen
dc.subjectMice, Knockouten
dc.subjectMiceen
dc.subjectPotassiumen
dc.subjectSodiumen
dc.subjectIon Transporten
dc.subjectAction Potentialsen
dc.subjectAgingen
dc.subjectArrhythmias, Cardiacen
dc.subjectPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaen
dc.titleCardiomyocyte ionic currents in intact young and aged murine Pgc-1β-/- atrial preparations.en
dc.typeArticle
prism.endingPage9
prism.publicationDate2018en
prism.publicationNameMechanisms of ageing and developmenten
prism.startingPage1
prism.volume169en
dc.identifier.doi10.17863/CAM.20172
dcterms.dateAccepted2017-11-28en
rioxxterms.versionofrecord10.1016/j.mad.2017.11.016en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2018-01en
dc.contributor.orcidSmyth, Robert [0000-0001-9482-5123]
dc.contributor.orcidJeevaratnam, Kamalan [0000-0002-6232-388X]
dc.contributor.orcidHuang, Christopher [0000-0001-9553-6112]
dc.identifier.eissn1872-6216
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/M001288/1)
pubs.funder-project-idBritish Heart Foundation (PG/14/79/31102)
pubs.funder-project-idWELLCOME TRUST (105727/Z/14/Z)
pubs.funder-project-idBritish Heart Foundation (PG/15/12/31280)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International