000057861 001__ 57861
000057861 005__ 20190529115205.0
000057861 0247_ $$2doi$$a10.1371/journal.pone.0105897
000057861 0248_ $$2sideral$$a88499
000057861 037__ $$aART-2014-88499
000057861 041__ $$aeng
000057861 100__ $$0(orcid)0000-0003-4273-5403$$aSanchez, Carlos
000057861 245__ $$aInter-subject variability in human atrial action potential in sinus rhythm versus chronic atrial fibrillation
000057861 260__ $$c2014
000057861 5060_ $$aAccess copy available to the general public$$fUnrestricted
000057861 5203_ $$aAims: Human atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR) and chronic atrial fibrillation (cAF) patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP) recorded in 363 patients both under SR and cAF conditions.
Methods and Results: Human AP recordings in atrial trabeculae (n?=?469) from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in GK1, GKur and Gto, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in IK1 and INaK underlies variability in APD90, variability in IKur, ICaL and INaK modulates variability in APD50 and combined variability in Ito and IKur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by IK1 and either INaK or INaCa depending on the model.
Conclusion: Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in human atrial AP duration and morphology in SR versus cAF.
000057861 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/TEC2010-19410$$9info:eu-repo/grantAgreement/EC/FP7/261057/EU/The European Network for Translational Research in Atrial Fibrillation/EUTRAF
000057861 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000057861 590__ $$a3.234$$b2014
000057861 591__ $$aMULTIDISCIPLINARY SCIENCES$$b9 / 57 = 0.158$$c2014$$dQ1$$eT1
000057861 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000057861 700__ $$aBueno-Orovio, Alfonso
000057861 700__ $$aWettwer, Erich
000057861 700__ $$aLoose, Simone
000057861 700__ $$aSimon, Jana
000057861 700__ $$aRavens, Ursula
000057861 700__ $$0(orcid)0000-0002-1960-407X$$aPueyo, Esther$$uUniversidad de Zaragoza
000057861 700__ $$aRodriguez, Blanca
000057861 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000057861 773__ $$g9, 8 (2014), e105897 [14 pp]$$pPLoS One$$tPLoS ONE$$x1932-6203
000057861 8564_ $$s3919560$$uhttps://zaguan.unizar.es/record/57861/files/texto_completo.pdf$$yVersión publicada
000057861 8564_ $$s119446$$uhttps://zaguan.unizar.es/record/57861/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000057861 909CO $$ooai:zaguan.unizar.es:57861$$particulos$$pdriver
000057861 951__ $$a2019-05-29-11:38:02
000057861 980__ $$aARTICLE