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Systematic characterization of the ionic basis of rabbit cellular electrophysiology using two ventricular models

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Systematic characterization of the ionic basis of rabbit cellular electrophysiology using two ventricular models

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dc.contributor.author Romero Pérez, Lucia es_ES
dc.contributor.author Carbonell Pascual, Beatriz es_ES
dc.contributor.author Trenor Gomis, Beatriz Ana es_ES
dc.contributor.author Rodríguez, Blanca es_ES
dc.contributor.author Saiz Rodríguez, Francisco Javier es_ES
dc.contributor.author Ferrero De Loma-Osorio, José María es_ES
dc.date.accessioned 2020-10-15T03:31:28Z
dc.date.available 2020-10-15T03:31:28Z
dc.date.issued 2011-10 es_ES
dc.identifier.issn 0079-6107 es_ES
dc.identifier.uri http://hdl.handle.net/10251/151876
dc.description.abstract [EN] Several mathematical models of rabbit ventricular action potential (AP) have been proposed to investigate mechanisms of arrhythmias and excitation-contraction coupling. Our study aims at systematically characterizing how ionic current properties modulate the main cellular biomarkers of arrhythmic risk using two widely-used rabbit ventricular models, and comparing simulation results using the two models with experimental data available for rabbit. A sensitivity analysis of AP properties, Ca(2+) and Na(+) dynamics, and their rate dependence to variations (+/- 15% and +/- 30%) in the main transmembrane current conductances and kinetics was performed using the Shannon et al. (2004) and the Mahajan et al. (2008a,b) AP rabbit models. The effects of severe transmembrane current blocks (up to 100%) on steady-state AP and calcium transients, and AP duration (APD) restitution curves were also simulated using both models. Our simulations show that, in both virtual rabbit cardiomyocytes, APD is significantly modified by most repolarization currents, AP triangulation is regulated mostly by the inward rectifier K(+) current (I(K1)) whereas APD rate adaptation as well as [Na(+)](i) rate dependence is influenced by the Na(+)/K(+) pump current (I(NaK)). In addition, steady-state [Ca(2+)](i) levels, APD restitution properties and [Ca(2+)](i); rate dependence are strongly dependent on I(NaK), the L-Type Ca(2+) current (I(CaL)) and the Na(+)/Ca(2+) exchanger current (I(NaCa)), although the relative role of these currents is markedly model dependent. Furthermore, our results show that simulations using both models agree with many experimentally-reported electrophysiological characteristics. However, our study shows that the Shannon et al. model mimics rabbit electrophysiology more accurately at normal pacing rates, whereas Mahajan et al. model behaves more appropriately at faster rates. Our results reinforce the usefulness of sensitivity analysis for further understanding of cellular electrophysiology and validation of cardiac AP models. es_ES
dc.description.sponsorship This work was partially supported by the European Commission preDiCT grant (DG INFSO-224381), Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica del Ministerio de Ciencia e Innovación of Spain (TEC2008-02090, TIN2004-03602), Programa de Apoyo a la Investigación y Desarrollo (PAID-06-09-2843)de la Universidad Politécnica de Valencia, Dirección General de Política Científica de la Generalitat Valenciana (GV/2010/078), a Consellería de Educación de la Generalitat Valenciana grant (BEST/2010/102) (to J.M.F), a Universidad Politécnica de Valencia grant (PAID-00-10) (to L.R.) and an UK Medical Research Council Career Development Award (to B.R.) es_ES
dc.language Inglés es_ES
dc.publisher Elsevier es_ES
dc.relation EC/DG INFSO-224381 es_ES
dc.relation GV/BEST/2010/102 es_ES
dc.relation UPV/PAID-00-10 es_ES
dc.relation MRC/G0700278 es_ES
dc.relation MINISTERIO DE EDUCACION /TEC2008-02090 es_ES
dc.relation UPV-VIN/PAID-06-09-2843 es_ES
dc.relation GENERALITAT VALENCIANA/GV/2010/078 es_ES
dc.relation.ispartof Progress in Biophysics and Molecular Biology es_ES
dc.rights Reserva de todos los derechos es_ES
dc.subject Biological variability es_ES
dc.subject Ionic current es_ES
dc.subject Model validation es_ES
dc.subject Arrhythmia es_ES
dc.subject Computer simulation es_ES
dc.subject.classification TECNOLOGIA ELECTRONICA es_ES
dc.title Systematic characterization of the ionic basis of rabbit cellular electrophysiology using two ventricular models es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1016/j.pbiomolbio.2011.06.012 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/224381/EU/Computational Prediction of Drug Cardiac Toxicity/ es_ES
dc.rights.accessRights Cerrado es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica es_ES
dc.description.bibliographicCitation Romero Pérez, L.; Carbonell Pascual, B.; Trenor Gomis, BA.; Rodríguez, B.; Saiz Rodríguez, FJ.; Ferrero De Loma-Osorio, JM. (2011). Systematic characterization of the ionic basis of rabbit cellular electrophysiology using two ventricular models. Progress in Biophysics and Molecular Biology. 107(1):60-73. https://doi.org/10.1016/j.pbiomolbio.2011.06.012 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.1016/j.pbiomolbio.2011.06.012 es_ES
dc.description.upvformatpinicio 60 es_ES
dc.description.upvformatpfin 73 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 107 es_ES
dc.description.issue 1 es_ES
dc.identifier.pmid 21749896 es_ES
dc.relation.pasarela S\212293 es_ES
dc.contributor.funder European Commission es_ES
dc.contributor.funder Generalitat Valenciana es_ES
dc.contributor.funder Ministerio de Educación es_ES
dc.contributor.funder Universitat Politècnica de València es_ES
dc.contributor.funder Medical Research Council, Reino Unido es_ES


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