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dc.contributor.authorLugo Vélez, Carlos Antonio
dc.contributor.authorRodríguez Cantalapiedra, Inma
dc.contributor.authorPeñaranda Ayllón, Angelina
dc.contributor.authorHove-Madsen, Leif
dc.contributor.authorEchebarría Domínguez, Blas
dc.contributor.otherUniversitat Politècnica de Catalunya. Departament de Física Aplicada
dc.identifier.citationLugo, C.A. [et al.]. Are SR Ca content fluctuations or SR refractoriness the key to atrial cardiac alternans?: insights from a human atrial model. "American journal of physiology. Heart and circulatory physiology", 01 Juny 2014, vol. 306, núm. 11, p. H1540-H1552.
dc.description.abstractDespite the important role of electromechanical alternans in cardiac arrhythmogenesis, its molecular origin is not well understood. The appearance of calcium alternans has often been associated to fluctuations in the sarcoplasmic reticulum (SR) Ca loading. However, cytosolic calcium alternans observed without concurrent oscillations in the SR Ca content suggests an alternative mechanism related to a dysfunction in the dynamics of the ryanodine receptor (RyR2). We have investigated the effect of SR release refractoriness in the appearance of alternans, using a mathematical model of a single human atrial cell, based on the model by Nygren et al. (30), where we modified the dynamics of the RyR2 and of SR Ca release. The genesis of calcium alternans was studied stimulating the cell for different periods and values of the RyR2 recovery time from inactivation. At fast rates cytosolic calcium alternans were obtained without concurrent SR Ca content fluctuations. A transition from regular response to alternans was also observed, changing the recovery time from inactivation of the RyR2. This transition was found to be hysteretic, so for a given set of parameters different responses were observed. We then studied the relevance of RyR2 refractoriness for the generation of alternans, reproducing the same protocols as in recent experiments. In particular, restitution of Ca release during alternans was studied with a S1S2 protocol, obtaining a different response if the S2 stimulation was given after a long or a short release. We show that the experimental results can be explained by RyR2 refractoriness, arising from a slow RyR2 recovery from inactivation, stressing the role of the RyR2 in the genesis of alternans.
dc.format.extent13 p.
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Spain
dc.subjectÀrees temàtiques de la UPC::Física
dc.subject.lcshSarcoplasmic reticulum
dc.subject.lcshMathematical models
dc.subject.lcshHeart failure
dc.subject.otherelectromechanical alternans
dc.subject.othercalcium dynamics
dc.subject.otherryanodine receptor
dc.subject.otherSR calcium release refractoriness
dc.titleAre SR Ca content fluctuations or SR refractoriness the key to atrial cardiac alternans?: insights from a human atrial model
dc.subject.lemacRianodina -- Receptors
dc.subject.lemacReticle sarcoplasmàtic
dc.subject.lemacModels matemàtics
dc.subject.lemacInsuficiència cardíaca
dc.contributor.groupUniversitat Politècnica de Catalunya. GICITED - Grup Interdiciplinari de Ciència i Tecnologia en l'Edificació
dc.contributor.groupUniversitat Politècnica de Catalunya. NOLIN - Física No-Lineal i Sistemes Fora de l'Equilibri
dc.rights.accessRestricted access - publisher's policy
dc.description.versionPostprint (author’s final draft)
local.citation.authorLugo, C.A.; Rodriguez, I.; Peñaranda, A.; Hove-Madsen, L.; Echebarria, B.
local.citation.publicationNameAmerican journal of physiology. Heart and circulatory physiology

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