2019
Cardiomyocyte-Specific STIM1 (Stromal Interaction Molecule 1) Depletion in the Adult Heart Promotes the Development of Arrhythmogenic Discordant Alternans
Cacheux M, Strauss B, Raad N, Ilkan Z, Hu J, Benard L, Feske S, Hulot JS, Akar FG. Cardiomyocyte-Specific STIM1 (Stromal Interaction Molecule 1) Depletion in the Adult Heart Promotes the Development of Arrhythmogenic Discordant Alternans. Circulation Arrhythmia And Electrophysiology 2019, 12: e007382-e007382. PMID: 31726860, PMCID: PMC6867678, DOI: 10.1161/circep.119.007382.Peer-Reviewed Original ResearchConceptsVT/VFAPD alternansStore-operated CaVentricular tachycardia/ventricular fibrillationOptical action potential mappingAdult heartVT/Adult murine modelDiscordant alternansConduction velocity slowingSarcoplasmic reticulum CaArrhythmogenic discordant alternansInitial beatsEarly mortalityFlox/Poor survivalVentricular fibrillationDiscordant APD alternansMurine modelCardiac hypertrophyConduction velocityLittermate controlsAdult miceRapid pacingElectrophysiological substrate
2015
LKB1 deletion causes early changes in atrial channel expression and electrophysiology prior to atrial fibrillation
Kim GE, Ross JL, Xie C, Su KN, Zaha VG, Wu X, Palmeri M, Ashraf M, Akar JG, Russell KS, Akar FG, Young LH. LKB1 deletion causes early changes in atrial channel expression and electrophysiology prior to atrial fibrillation. Cardiovascular Research 2015, 108: 197-208. PMID: 26378152, PMCID: PMC4571838, DOI: 10.1093/cvr/cvv212.Peer-Reviewed Original ResearchConceptsLiver kinase B1Protein kinaseLKB1 deletionMetabolic regulator AMPAtrial fibrillationChannel expressionMHC-CreElectrophysiological functionKnockout mouse modelRelated kinasesLKB1 pathwayGene expressionPerpetuation of AFKinase B1Neonatal atrial myocytesΑMHC-CreKinasePostnatal day 1Patch-clamp recordingsAtrial growthWeeks of ageDeletionSodium current densityAction potential generationSpecific role
2011
Disruption of Hexokinase II–Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis
Smeele KM, Southworth R, Wu R, Xie C, Nederlof R, Warley A, Nelson JK, van Horssen P, van den Wijngaard JP, Heikkinen S, Laakso M, Koeman A, Siebes M, Eerbeek O, Akar FG, Ardehali H, Hollmann MW, Zuurbier CJ. Disruption of Hexokinase II–Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis. Circulation Research 2011, 108: 1165-1169. PMID: 21527739, DOI: 10.1161/circresaha.111.244962.Peer-Reviewed Original ResearchConceptsIschemic preconditioningWild-type heartsCardiac functionProtective effectHKII levelsBaseline cardiac functionIschemia-reperfusion injuryNormal cardiac functionMitochondrial permeability transition openingContractile impairmentReperfusion injuryAcute reductionCardiac necrosisMyocardial functionGlycolytic enzymes hexokinaseCardiac contractionMild mitochondrial uncouplingMembrane depolarizationMitochondrial membrane depolarizationHKIIMitochondrial hexokinaseControl peptideHeartPreconditioningTissue disruption