2010
Ultrastructure and Regulation of Lateralized Connexin43 in the Failing Heart
Hesketh GG, Shah MH, Halperin VL, Cooke CA, Akar FG, Yen TE, Kass DA, Machamer CE, Van Eyk JE, Tomaselli GF. Ultrastructure and Regulation of Lateralized Connexin43 in the Failing Heart. Circulation Research 2010, 106: 1153-1163. PMID: 20167932, PMCID: PMC2896878, DOI: 10.1161/circresaha.108.182147.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagyConnexin 43Disease Models, AnimalDogsGap JunctionsHeart FailureHeart VentriclesHeLa CellsHumansMembrane MicrodomainsMicroscopy, ConfocalMicroscopy, Electron, TransmissionMicrotubule-Associated ProteinsMyocardiumPhosphorylationRatsRats, Sprague-DawleyRecombinant Fusion ProteinsTransfectionConceptsGFP-LC3Gap junctionsLateral membranesDistinct phosphorylated formsGap junction turnoverGap junction internalizationForm of LC3Internalized gap junctionsGap junction proteinJunction turnoverSubcellular locationBiochemical regulationCellular pathwaysMultilamellar membrane structuresEndogenous Cx43Phosphorylated formNeonatal rat ventricular myocytesHeLa cellsIntracellular Cx43Membrane structureJunction proteinsCx43ProteinPotential therapeutic implicationsConnexin43
2009
Electrophysiological Consequences of Dyssynchronous Heart Failure and Its Restoration by Resynchronization Therapy
Aiba T, Hesketh GG, Barth AS, Liu T, Daya S, Chakir K, Dimaano VL, Abraham TP, O'Rourke B, Akar FG, Kass DA, Tomaselli GF. Electrophysiological Consequences of Dyssynchronous Heart Failure and Its Restoration by Resynchronization Therapy. Circulation 2009, 119: 1220-1230. PMID: 19237662, PMCID: PMC2703676, DOI: 10.1161/circulationaha.108.794834.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsBundle-Branch BlockCalciumCalcium ChannelsCoronary CirculationDogsEchocardiographyElectrocardiographyHeart FailureHomeostasisKv Channel-Interacting ProteinsMaleMyocytes, CardiacPacemaker, ArtificialPatch-Clamp TechniquesPotassium Channels, Inwardly RectifyingRNA, MessengerSarcoplasmic Reticulum Calcium-Transporting ATPasesShal Potassium ChannelsConceptsCardiac resynchronization therapyAction potential durationRight atrial pacingCalcium transient amplitudeHeart failurePotential durationResynchronization therapyAtrial pacingElectrophysiological consequencesLeft bundle-branch ablationTransient amplitudeSarcoplasmic reticulumWhole-cell patch clampDyssynchronous heart failureProtein levelsIon channel remodelingSame pacing rateLeft ventricular anteriorQuantitative polymerase chain reactionSurvival benefitBiventricular pacingVentricular arrhythmiasDyssynchronous contractionPolymerase chain reactionElectrophysiological changes
2008
Key pathways associated with heart failure development revealed by gene networks correlated with cardiac remodeling
Gao Z, Barth AS, DiSilvestre D, Akar FG, Tian Y, Tanskanen A, Kass DA, Winslow RL, Tomaselli GF. Key pathways associated with heart failure development revealed by gene networks correlated with cardiac remodeling. Physiological Genomics 2008, 35: 222-230. PMID: 18780759, PMCID: PMC2585017, DOI: 10.1152/physiolgenomics.00100.2007.Peer-Reviewed Original Research
2007
Dynamic changes in conduction velocity and gap junction properties during development of pacing-induced heart failure
Akar FG, Nass RD, Hahn S, Cingolani E, Shah M, Hesketh GG, DiSilvestre D, Tunin RS, Kass DA, Tomaselli GF. Dynamic changes in conduction velocity and gap junction properties during development of pacing-induced heart failure. AJP Heart And Circulatory Physiology 2007, 293: h1223-h1230. PMID: 17434978, DOI: 10.1152/ajpheart.00079.2007.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsCardiac Pacing, ArtificialConnexin 43Disease Models, AnimalDogsDown-RegulationGap JunctionsHeart Conduction SystemHeart FailureMalePhosphorylationProtein IsoformsTachycardia, VentricularTime FactorsVentricular Function, LeftVentricular PressureVentricular RemodelingConceptsEnd-stage heart failureHeart failureConduction velocityMechanical dysfunctionCV slowingPacing-induced heart failureDevelopment of HFOnset of HFMechanical functionCx43 isoformConduction abnormalitiesCx43 lateralizationAdvanced stageBaseline levelsMyocardial preparationsPhosphorylation of Cx43High-resolution optical mappingSustained downregulationMarked increaseDephosphorylated Cx43LVEDPGap junction propertiesConduction changesDysfunctionTime course
2005
Abnormal conduction and repolarization in late-activated myocardium of dyssynchronously contracting hearts
Spragg DD, Akar FG, Helm RH, Tunin RS, Tomaselli GF, Kass DA. Abnormal conduction and repolarization in late-activated myocardium of dyssynchronously contracting hearts. Cardiovascular Research 2005, 67: 77-86. PMID: 15885674, DOI: 10.1016/j.cardiores.2005.03.008.Peer-Reviewed Original ResearchConceptsAction potential durationConduction velocityRefractory periodElectrophysiological remodelingArrhythmia susceptibilityIntraventricular conduction delayLeft ventricular dyssynchronyGap junction protein expressionJunction protein expressionCalcium cycling proteinsTotal expressionDyssynchronous heartsLV dysfunctionMechanical dyssynchronyUntreated dogsVentricular dyssynchronyCardiac dyssynchronyControl dogsLateral LVRadiofrequency ablationAnterior wallConduction delayDyssynchronyMyocardial segmentsPotential durationMolecular mechanisms underlying K+ current downregulation in canine tachycardia-induced heart failure
Akar FG, Wu RC, Juang GJ, Tian Y, Burysek M, DiSilvestre D, Xiong W, Armoundas AA, Tomaselli GF. Molecular mechanisms underlying K+ current downregulation in canine tachycardia-induced heart failure. AJP Heart And Circulatory Physiology 2005, 288: h2887-h2896. PMID: 15681701, DOI: 10.1152/ajpheart.00320.2004.Peer-Reviewed Original Research
2004
Mechanisms Underlying Conduction Slowing and Arrhythmogenesis in Nonischemic Dilated Cardiomyopathy
Akar FG, Spragg DD, Tunin RS, Kass DA, Tomaselli GF. Mechanisms Underlying Conduction Slowing and Arrhythmogenesis in Nonischemic Dilated Cardiomyopathy. Circulation Research 2004, 95: 717-725. PMID: 15345654, DOI: 10.1161/01.res.0000144125.61927.1c.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsArrhythmias, CardiacBlotting, WesternCadherinsCardiac Pacing, ArtificialCardiomyopathy, DilatedCell SizeConnexin 43DogsFibrosisGap JunctionsHeart Conduction SystemMicroscopy, ConfocalMicroscopy, FluorescenceMyocardiumMyocytes, CardiacNeural ConductionPatch-Clamp TechniquesPhosphorylationProtein Processing, Post-TranslationalSubcellular FractionsHeterogeneous connexin43 expression produces electrophysiological heterogeneities across ventricular wall
Poelzing S, Akar FG, Baron E, Rosenbaum DS. Heterogeneous connexin43 expression produces electrophysiological heterogeneities across ventricular wall. AJP Heart And Circulatory Physiology 2004, 286: h2001-h2009. PMID: 14704225, DOI: 10.1152/ajpheart.00987.2003.Peer-Reviewed Original Research
2003
Phenotypic differences in transient outward K+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular Ito
Akar FG, Wu RC, Deschenes I, Armoundas AA, Piacentino V, Houser SR, Tomaselli GF. Phenotypic differences in transient outward K+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular Ito. AJP Heart And Circulatory Physiology 2003, 286: h602-h609. PMID: 14527940, DOI: 10.1152/ajpheart.00673.2003.Peer-Reviewed Original ResearchConceptsTransient outwardPhenotypic differencesKv channel-interacting proteinsIndependent transient outwardChannel-interacting proteinsProtein chemical techniquesSteady-state inactivationCanine ventricular myocytesWestern blot analysisElectrical remodelingChannel subunit genesMonoexponential time coursePharmacological sensitivityVentricular repolarizationCardiac diseaseElectrophysiological roleCanine ventricularHuman cardiac diseasePosttranslational modificationsVentricular myocytesSubunit genePharmacological propertiesDiseased heartPhenotypic propertiesOxidative stressTransmural Electrophysiological Heterogeneities Underlying Arrhythmogenesis in Heart Failure
Akar FG, Rosenbaum DS. Transmural Electrophysiological Heterogeneities Underlying Arrhythmogenesis in Heart Failure. Circulation Research 2003, 93: 638-645. PMID: 12933704, DOI: 10.1161/01.res.0000092248.59479.ae.Peer-Reviewed Original ResearchConceptsPolymorphic ventricular tachycardiaHeart failureQT interval prolongationQT intervalM cellsConduction blockAPD prolongationTransmural wallAction potential duration prolongationRapid ventricular pacingTransmural heterogeneityFunctional conduction blockVentricular tachyarrhythmiasPremature impulsesSubepicardial zoneVentricular pacingVentricular tachycardiaHF phenotypesDuration prolongationCanine wedge preparationSelective prolongationDecremental conductionAction potentialsOptical action potentialsVentricular wall
2002
Unique Topographical Distribution of M Cells Underlies Reentrant Mechanism of Torsade de Pointes in the Long-QT Syndrome
Akar FG, Yan GX, Antzelevitch C, Rosenbaum DS. Unique Topographical Distribution of M Cells Underlies Reentrant Mechanism of Torsade de Pointes in the Long-QT Syndrome. Circulation 2002, 105: 1247-1253. PMID: 11889021, DOI: 10.1161/hc1002.105231.Peer-Reviewed Original ResearchConceptsLong QT syndromeSpecific ion channel mutationsCongenital long QT syndromeM cellsQT interval prolongationIon channel mutationsInterval prolongationReentrant mechanismTdP arrhythmiasConduction blockCanine wedge preparationReentrant circuitTransmural dispersionLeft ventricleAction potentialsTransmural wallIntact myocardiumTopographical distributionChannel mutationsWedge preparationsMidmyocardial cellsRepolarizationLQT2Cellular basisElectrical instability
2000
Cellular basis for dispersion of repolarization underlying reentrant arrhythmias
Akar F, Laurita K, Rosenbaum D. Cellular basis for dispersion of repolarization underlying reentrant arrhythmias. Journal Of Electrocardiology 2000, 33: 23-31. PMID: 11265727, DOI: 10.1054/jelc.2000.20313.Peer-Reviewed Original Research