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dc.contributor.authorTinaquero, David
dc.contributor.authorCrespo-García, Teresa
dc.contributor.authorUtrilla, Raquel G
dc.contributor.authorNieto-Marín, Paloma
dc.contributor.authorGonzález-Guerra, Andrés
dc.contributor.authorRubio-Alarcón, Marcos
dc.contributor.authorCámara-Checa, Anabel
dc.contributor.authorDago, María
dc.contributor.authorMatamoros, Marcos
dc.contributor.authorPérez-Hernández, Marta
dc.contributor.authorTamargo, María
dc.contributor.authorCebrián, Jorge
dc.contributor.authorJalife, Jose 
dc.contributor.authorTamargo, Juan
dc.contributor.authorBernal, Juan Antonio 
dc.contributor.authorCaballero, Ricardo
dc.contributor.authorDelpón, Eva
dc.date.accessioned2020-09-22T06:28:28Z
dc.date.available2020-09-22T06:28:28Z
dc.date.issued2020-07
dc.identifier.citationSci Rep. 2020; 10(1):10707es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/11056
dc.description.abstractSynapse-Associated Protein 97 (SAP97) is an anchoring protein that in cardiomyocytes targets to the membrane and regulates Na+ and K+ channels. Here we compared the electrophysiological effects of native (WT) and p.P888L SAP97, a common polymorphism. Currents were recorded in cardiomyocytes from mice trans-expressing human WT or p.P888L SAP97 and in Chinese hamster ovary (CHO)-transfected cells. The duration of the action potentials and the QT interval were significantly shorter in p.P888L-SAP97 than in WT-SAP97 mice. Compared to WT, p.P888L SAP97 significantly increased the charge of the Ca-independent transient outward (Ito,f) current in cardiomyocytes and the charge crossing Kv4.3 channels in CHO cells by slowing Kv4.3 inactivation kinetics. Silencing or inhibiting Ca/calmodulin kinase II (CaMKII) abolished the p.P888L-induced Kv4.3 charge increase, which was also precluded in channels (p.S550A Kv4.3) in which the CaMKII-phosphorylation is prevented. Computational protein-protein docking predicted that p.P888L SAP97 is more likely to form a complex with CaMKII than WT. The Na+ current and the current generated by Kv1.5 channels increased similarly in WT-SAP97 and p.P888L-SAP97 cardiomyocytes, while the inward rectifier current increased in WT-SAP97 but not in p.P888L-SAP97 cardiomyocytes. The p.P888L SAP97 polymorphism increases the Ito,f, a CaMKII-dependent effect that may increase the risk of arrhythmias.es_ES
dc.description.sponsorshipThis work was funded by: Ministerio de Economía y Competitividad [SAF2017-88116-P; BFU2016-75144-R (JAB)]; Comunidad Autónoma de Madrid [B2017/BMD-3738; 2018-T2/BMD-10724 (JC)], Comunidad Autónoma de Madrid and Universidad Complutense de Madrid [PR65/19-22358 (JC)] European Structural and Investment Funds (ESIF); Instituto de Salud Carlos III [PI16/00398]; The Spanish Society of Cardiology.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Group es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleThe p.P888L SAP97 polymorphism increases the transient outward current (Ito,f) and abbreviates the action potential duration and the QT interval.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID32612162es_ES
dc.format.volume10es_ES
dc.format.number1es_ES
dc.format.page10707es_ES
dc.identifier.doi10.1038/s41598-020-67109-zes_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderComplutense University of Madrid (España) 
dc.contributor.funderUnión Europea. Fondos Estructurales y de Inversión Europeos (ESIF) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderSociedad Española de Cardiología 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2045-2322es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41598-020-67109-zes_ES
dc.identifier.journalScientific reportses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Cardiomiopatías de origen genéticoes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Arritmias Cardíacases_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2017-88116-Pes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2016-75144-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI16/00398es_ES
dc.rights.accessRightsopen accesses_ES


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