2022
Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation
Su KN, Ma Y, Cacheux M, Ilkan Z, Raad N, Muller GK, Wu X, Guerrera N, Thorn SL, Sinusas AJ, Foretz M, Viollet B, Akar JG, Akar FG, Young LH. Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation. JCI Insight 2022, 7: e141213. PMID: 35451373, PMCID: PMC9089788, DOI: 10.1172/jci.insight.141213.Peer-Reviewed Original ResearchConceptsTranscription factorsKey transcription factorMaster metabolic regulatorIon channel subunitsGap junction proteinTranscriptional reprogrammingAMPK deletionProtein kinaseBiological functionsTranscriptional downregulationMetabolic regulatorChannel subunitsIon channelsAMPK expressionMetabolic stressAtrial fibrillationAMPKJunction proteinsElectrical excitabilityHomeostatic roleStructural remodelingConnexinsAtrial ion channelsRemodelingDownregulation
2015
The Mitochondrial Translocator Protein and Arrhythmogenesis in Ischemic Heart Disease
Motloch LJ, Hu J, Akar FG. The Mitochondrial Translocator Protein and Arrhythmogenesis in Ischemic Heart Disease. Oxidative Medicine And Cellular Longevity 2015, 2015: 234104. PMID: 25918579, PMCID: PMC4397036, DOI: 10.1155/2015/234104.Peer-Reviewed Original ResearchConceptsIschemic heart diseaseHeart diseaseTranslocator proteinAcute ischemia-reperfusion injuryReactive oxygen speciesIschemia-reperfusion injuryMultiple organ systemsExcitation-contraction couplingMultiple cardiovascular disordersPermeability transition poreRole of TSPOMyocardial infarctionInflammatory processDiverse pathophysiological processesImmune responseCardiovascular disordersTherapeutic targetPathophysiological processesOrgan systemsDiagnostic markerMitochondrial dysfunctionDiseaseAbundant expressionMitochondrial translocator proteinROS release
2014
Gene therapies for arrhythmias in heart failure
Akar FG, Hajjar RJ. Gene therapies for arrhythmias in heart failure. Pflügers Archiv - European Journal Of Physiology 2014, 466: 1211-1217. PMID: 24566976, PMCID: PMC4070506, DOI: 10.1007/s00424-014-1485-3.Peer-Reviewed Original Research
2008
Mechanisms of Disease: ion channel remodeling in the failing ventricle
Nass RD, Aiba T, Tomaselli GF, Akar FG. Mechanisms of Disease: ion channel remodeling in the failing ventricle. Nature Clinical Practice Cardiovascular Medicine 2008, 5: 196-207. PMID: 18317475, DOI: 10.1038/ncpcardio1130.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2007
Regulation of ion channels and arrhythmias in the ischemic heart
Akar JG, Akar FG. Regulation of ion channels and arrhythmias in the ischemic heart. Journal Of Electrocardiology 2007, 40: s37-s41. PMID: 17993326, DOI: 10.1016/j.jelectrocard.2007.05.020.Peer-Reviewed Original ResearchConceptsIschemic injuryElectrophysiological changesIschemic heart diseaseBest treatment strategyCoronary eventsReperfusion phaseVentricular arrhythmiasIschemic episodesHeart diseaseLeading causeElectrical dysfunctionTreatment strategiesIschemic heartMetabolic substratesPatientsArrhythmiasKey cellularTime courseInjuryIon channelsHeartDysfunctionMortalityDiseaseMitochondrial Ion Channels in Cardiac Function and Dysfunction
O'Rourke B, Cortassa S, Akar F, Aon M. Mitochondrial Ion Channels in Cardiac Function and Dysfunction. Novartis Foundation Symposia 2007, 287: 140-156. PMID: 18074636, PMCID: PMC2692520, DOI: 10.1002/9780470725207.ch10.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMitochondrial ion channelsIon channelsReactive oxygen species (ROS) signalsNumerous signaling pathwaysBurst of ROSMitochondrial networkMitochondrial physiologyPlasma membraneSpecies signalSignaling pathwaysCellular activitiesCellular targetsMitochondrial functionEnergy transductionMitochondriaVast modificationsPhysiological conditionsOrgan levelDisease developmentPotential therapeutic interventionsWidespread effectsImportant targetSurprising insightsKey roleCenter of organizations
2006
Bioartificial Sinus Node Constructed via In Vivo Gene Transfer of an Engineered Pacemaker HCN Channel Reduces the Dependence on Electronic Pacemaker in a Sick-Sinus Syndrome Model
Tse HF, Xue T, Lau CP, Siu CW, Wang K, Zhang QY, Tomaselli GF, Akar FG, Li RA. Bioartificial Sinus Node Constructed via In Vivo Gene Transfer of an Engineered Pacemaker HCN Channel Reduces the Dependence on Electronic Pacemaker in a Sick-Sinus Syndrome Model. Circulation 2006, 114: 1000-1011. PMID: 16923751, DOI: 10.1161/circulationaha.106.615385.Peer-Reviewed Original ResearchAnimalsArrhythmias, CardiacBioartificial OrgansCyclic Nucleotide-Gated Cation ChannelsDisease Models, AnimalElectrophysiologyGene Transfer TechniquesGuinea PigsHeart RateHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsIon ChannelsMicePacemaker, ArtificialPotassium ChannelsSick Sinus SyndromeSinoatrial NodeSwineSwine, Miniature
2005
The mitochondrial origin of postischemic arrhythmias
Akar FG, Aon MA, Tomaselli GF, O'Rourke B. The mitochondrial origin of postischemic arrhythmias. Journal Of Clinical Investigation 2005, 115: 3527-3535. PMID: 16284648, PMCID: PMC1280968, DOI: 10.1172/jci25371.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnionsArrhythmias, CardiacDose-Response Relationship, DrugElectrophysiologyGuinea PigsHeartIntracellular MembranesIon ChannelsIschemiaMembrane PotentialsMicroscopy, ConfocalMitochondria, HeartMyocardial IschemiaMyocardial ReperfusionMyocardial Reperfusion InjuryMyocardiumMyocytes, CardiacOscillometryReactive Oxygen SpeciesReceptors, GABA-AReperfusion InjuryTemperatureTime FactorsConceptsAction potentialsVentricular fibrillationPostischemic functional recoveryIschemic heart diseaseGuinea pig heartsNew therapeutic targetsAbnormal electrical activationPostischemic arrhythmiasReperfusion arrhythmiasFunctional recoveryGlobal ischemiaHeart diseaseBolus infusionArrhythmia preventionElectrophysiological changesAP shorteningControl heartsPostischemic heartsBenzodiazepine receptorsElectrophysiological substrateTherapeutic targetArrhythmiasReperfusionPig heartsMitochondrial benzodiazepine receptorIon channels as novel therapeutic targets in heart failure
Akar FG, Tomaselli GF. Ion channels as novel therapeutic targets in heart failure. Annals Of Medicine 2005, 37: 44-54. PMID: 15902846, DOI: 10.1080/07853890510007214.Peer-Reviewed Original ResearchConceptsHeart failureIon channel functionAnti-arrhythmic therapyLethal ventricular tachyarrhythmiasCalcium handling proteinsNovel therapeutic targetPublic health epidemicIon channel dysfunctionChannel functionVentricular tachyarrhythmiasTherapeutic targetChannel dysfunctionHandling proteinsSodium currentHealth epidemicNovel targetImpulse generationElectrical phenotypeIon channelsCurrent understandingTachyarrhythmiasFailureDysfunctionTherapyAbnormalities
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