Please use this identifier to cite or link to this item: https://repositorio.usj.es/handle/123456789/486

Title: Vascular Reactivity Profile of Novel KCa3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed
Authors: Olivan-Viguera, Aida ORCID RESEARCHERID
Valero Gracia, Marta Sofía ORCID SCOPUSID
Pinilla, Estéfano ORCID RESEARCHERID SCOPUSID
Amor, Sara SCOPUSID
García-Villalón, Ángel Luis SCOPUSID
Coleman, Nichole SCOPUSID
Laría, Celia SCOPUSID
Calvín-Tienza, Víctor SCOPUSID
García-Otín, Ángel Luis ORCID RESEARCHERID SCOPUSID
Fernández-Fernández, José Manuel ORCID SCOPUSID
Murillo, Mª Divina ORCID RESEARCHERID SCOPUSID
Gálvez, José Antonio ORCID SCOPUSID
Díaz-De-Villegas, Maŕia Dolores ORCID RESEARCHERID SCOPUSID
Badorrey, Ramón RESEARCHERID SCOPUSID
Simonsen, Ulf ORCID SCOPUSID
Rivera, Luis SCOPUSID
Wulff, Heike ORCID SCOPUSID
Köhler, Ralf ORCID SCOPUSID
Keywords: KCa3.1
Issue Date: 1-Mar-2019
Publisher: Blackwell Publishing Ltd
Citation: Oliván-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.12560
Abstract: Abstract: 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.
URI: https://repositorio.usj.es/handle/123456789/486
ISSN: 1742-7835
Appears in Collections:Artículos de revistas

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