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2020-08-04Zeitschriftenartikel DOI: 10.18452/22666
Modifications of sodium channel voltage dependence induce arrhythmia-favouring dynamics of cardiac action potentials
dc.contributor.authorRose, Pia
dc.contributor.authorSchleimer, Jan Hendrik
dc.contributor.authorSchreiber, Susanne
dc.date.accessioned2021-03-31T13:31:27Z
dc.date.available2021-03-31T13:31:27Z
dc.date.issued2020-08-04none
dc.identifier.urihttp://edoc.hu-berlin.de/18452/23273
dc.descriptionThis article was supported by the German Research Foundation (DFG) and the Open Access Publication Fund of Humboldt-Universität zu Berlin.none
dc.description.abstractHeart arrhythmia is a pathological condition where the sequence of electrical impulses in the heart deviates from the normal rhythm. It is often associated with specific channelopathies in cardiac tissue, yet how precisely the changes in ionic channels affect the electrical activity of cardiac cells is still an open question. Even though sodium channel mutations that underlie cardiac syndromes like the Long-Q-T and the Brugada-syndrome are known to affect a number of channel parameters simultaneously, previous studies have predominantly focused on the persistent late component of the sodium current as the causal explanation for an increased risk of heart arrhythmias in these cardiac syndromes. A systematic analysis of the impact of other important sodium channel parameters is currently lacking. Here, we investigate the reduced ten-Tusscher-model for single human epicardium ventricle cells and use mathematical bifurcation analysis to predict the dependence of the cardiac action potential on sodium channel activation and inactivation time-constants and voltage dependence. We show that, specifically, shifts of the voltage dependence of activation and inactivation curve can lead to drastic changes in the action potential dynamics, inducing oscillations of the membrane potential as well as bistability. Our results not only demonstrate a new way to induce multiple co-existing states of excitability (biexcitability) but also emphasize the critical role of the voltage dependence of sodium channel activation and inactivation curves for the induction of heart-arrhythmias.eng
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY 4.0) Attribution 4.0 Internationalger
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.ddc500 Naturwissenschaften und Mathematiknone
dc.titleModifications of sodium channel voltage dependence induce arrhythmia-favouring dynamics of cardiac action potentialsnone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/23273-5
dc.identifier.doihttp://dx.doi.org/10.18452/22666
dc.type.versionpublishedVersionnone
local.edoc.pages14none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
dc.description.versionPeer Reviewednone
dc.identifier.eissn1932-6203
dcterms.bibliographicCitation.doi10.1371/journal.pone.0236949
dcterms.bibliographicCitation.journaltitlePLOS ONEnone
dcterms.bibliographicCitation.volume15none
dcterms.bibliographicCitation.issue8none
dcterms.bibliographicCitation.articlenumbere0236949none
dcterms.bibliographicCitation.originalpublishernamePLOSnone
dcterms.bibliographicCitation.originalpublisherplaceSan Francisconone
bua.departmentLebenswissenschaftliche Fakultätnone

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