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dc.contributor.authorOlivan-Viguera, Aida-
dc.contributor.authorValero Gracia, Marta Sofía-
dc.contributor.authorPinilla, Estéfano-
dc.contributor.authorAmor, Sara-
dc.contributor.authorGarcía-Villalón, Ángel Luis-
dc.contributor.authorColeman, Nichole-
dc.contributor.authorLaría, Celia-
dc.contributor.authorCalvín-Tienza, Víctor-
dc.contributor.authorGarcía-Otín, Ángel Luis-
dc.contributor.authorFernández-Fernández, José Manuel-
dc.contributor.authorMurillo, Mª Divina-
dc.contributor.authorGálvez, José Antonio-
dc.contributor.authorDíaz-De-Villegas, Maŕia Dolores-
dc.contributor.authorBadorrey, Ramón-
dc.contributor.authorSimonsen, Ulf-
dc.contributor.authorRivera, Luis-
dc.contributor.authorWulff, Heike-
dc.contributor.authorKöhler, Ralf-
dc.date.accessioned2021-02-19T12:40:44Z-
dc.date.available2021-02-19T12:40:44Z-
dc.date.issued2019-03-01-
dc.identifier.citationOliván-Viguera, A., Valero, M.S., Pinilla, E., Amor, S., García-Villalón, Á.L., Coleman, N., Laría, C., Calvín-Tienza, V., García-Otín, Á.-L., Fernández-Fernández, J.M., Murillo, M.D., Gálvez, J.A., Díaz-De-Villegas, M.D., Badorrey, R., Simonsen, U., Rivera, L., Wulff, H., Köhler, R., 2016. Vascular Reactivity Profile of Novel KCa3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed. Basic & Clinical Pharmacology & Toxicology 119, 184–192.. doi:10.1111/bcpt.12560es_ES
dc.identifier.issn1742-7835es_ES
dc.identifier.urihttps://repositorio.usj.es/handle/123456789/486-
dc.description.abstractAbstract: Opening of intermediate-conductance calcium-activated potassium channels (KCa3.1) produces membrane hyperpolarization in the vascular endothelium. Here, we studied the ability of two new KCa3.1-selective positive-gating modulators, SKA111 and SKA-121, to (1) evoke porcine endothelial cell KCa3.1 membrane hyperpolarization, (2) induce endothelium-dependent and, particularly, endothelium-derived hyperpolarization (EDH)-type relaxation in porcine coronary arteries (PCA) and (3) influence coronary artery tone in isolated rat hearts. In whole-cell patch-clamp experiments on endothelial cells of PCA (PCAEC), KCa currents evoked by bradykinin (BK) were potentiated 7-fold by either SKA-111 or SKA-121 (both at 1 lM) and were blocked by a KCa3.1 blocker, TRAM-34. In membrane potential measurements, SKA-111 and SKA-121 augmented bradykinininduced hyperpolarization. Isometric tension measurements in large- and small-calibre PCA showed that SKA-111 and SKA-121 potentiated endothelium-dependent relaxation with intact NO synthesis and EDH-type relaxation to BK by 2-fold. Potentiation of the BK response was prevented by KCa3.1 inhibition. In Langendorff-perfused rat hearts, SKA-111 potentiated coronary vasodilation elicited by BK. In conclusion, our data show that positive-gating modulation of KCa3.1 channels improves BKinduced membrane hyperpolarization and endothelium-dependent relaxation in small and large PCA as well as in the coronary circulation of rats. Positive-gating modulators of KCa3.1 could be therapeutically useful to improve coronary blood flow and counteract impaired coronary endothelial dysfunction in cardiovascular disease.es_ES
dc.format.extent9 p.es_ES
dc.format.mimetypeapplication/pdfes_ES
dc.language.isoenges_ES
dc.publisherBlackwell Publishing Ltdes_ES
dc.relationThis work was supported by the Deutsche Forschungsgemeinschaft [KO1899/11-1 to RK]; the Danish Heart Foundation (to RK and US), European Community [FP7-PEOPLE Project 321721]; Department of Industry & Innovation, Government of Aragon [GIPASC-B105 to ALGO, RK, AOV]; and the Fondo de Investigaci?n Sanitaria, Instituto de Salud Carlos III [RIC RD12/0042/0014 Red HERACLES, to RK]. This study received Grant from the Government of Arag?n [GA E-102 to JAG, MDD, RB]; Grant of the Spanish Ministry of Economy and Competitiveness plus FEDER Funds [no SAF2012-31631 to LR and SAF2012-31089 to JMFF]; Grants from the National Institute of Neurological Disorders and Stroke [R21NS072585 to HW]; and from the National Heart, Lung & Blood Institute T32 Training Program in Basic and Translational Cardiovascular Science [T32HL086350 to NC].es_ES
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectKCa3.1es_ES
dc.titleVascular Reactivity Profile of Novel KCa3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bedes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.identifier.doiDOI: 10.1111/bcpt.12560es_ES
dc.rights.accessrightsinfo:eu-repo/semantics/openAccesses_ES
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