2021
Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation
Raad N, Bittihn P, Cacheux M, Jeong D, Ilkan Z, Ceholski D, Kohlbrenner E, Zhang L, Cai CL, Kranias EG, Hajjar RJ, Stillitano F, Akar FG. Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation. Circulation 2021, 144: 441-454. PMID: 34024116, PMCID: PMC8456417, DOI: 10.1161/circulationaha.119.043502.Peer-Reviewed Original ResearchConceptsHuman PLNRapid pacingInterventricular activation delayHumanized mouse modelAction potential prolongationLocal conduction blockSteep repolarization gradientsArrhythmogenic featuresMacroreentrant circuitHemodynamic changesElectric remodelingElectrophysiological remodelingRight ventricleVentricular tachycardiaPotential prolongationSudden deathConduction blockMouse modelAdult knockArrhythmia susceptibilityAdrenergic stimulationStructural remodelingArrhythmogenic phenotypeArrhythmia mechanismsRegulatory protein phospholamban
2008
Targeted deletion of kcne2 impairs ventricular repolarization via disruption of IK,slow1 and Ito,f
Roepke TK, Kontogeorgis A, Ovanez C, Xu X, Young JB, Purtell K, Goldstein PA, Christini DJ, Peters NS, Akar FG, Gutstein DE, Lerner DJ, Abbott GW. Targeted deletion of kcne2 impairs ventricular repolarization via disruption of IK,slow1 and Ito,f. The FASEB Journal 2008, 22: 3648-3660. PMID: 18603586, PMCID: PMC2537427, DOI: 10.1096/fj.08-110171.Peer-Reviewed Original ResearchConceptsAlpha subunitKv4 alpha subunitsAction potential durationVentricular action potential durationFunctional promiscuityVentricular membrane fractionsLong QT syndromeVentricular repolarizationAncillary subunitsWild typeNovel roleMembrane fractionKcne2 deletionKv1.5 proteinTargeted deletionSubunitsKcne2 disruptionMiRP1Cardiac roleProteinKCNE2DeletionKv1.5Sevoflurane anesthesiaDisruption