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dc.contributor.authorÁlvarez Miguel, Inés
dc.contributor.authorCidad Velasco, María del Pilar
dc.contributor.authorPérez García, María Teresa 
dc.contributor.authorLópez López, José Ramón 
dc.date.accessioned2020-12-21T13:58:55Z
dc.date.available2020-12-21T13:58:55Z
dc.date.issued2016
dc.identifier.citationThe Journal of Physiology, 2017, vol. 595, n. 5. p. 1497-1513es
dc.identifier.issn1469-7793es
dc.identifier.urihttp://uvadoc.uva.es/handle/10324/44482
dc.descriptionProducción Científicaes
dc.description.abstractIncreased vascular tone in essential hypertension involves a sustained rise in total peripheral resistance. A model has been proposed in which the combination of membrane depolarization and higher L‐type Ca2+ channel activity generates augmented Ca2+ influx into vascular smooth muscle cells (VSMCs), contraction and vasoconstriction. The search for culprit ion channels responsible for membrane depolarization has provided several candidates, including members of the canonical transient receptor potential (TRPC) family. TRPC3 and TRPC6 are diacylglycerol‐activated, non‐selective cationic channels contributing to stretch‐ or agonist‐induced depolarization. Conflicting information exists regarding changes in TRPC3/TRPC6 functional expression in hypertension. However, although TRPC3‐TRPC6 channels can heteromultimerize, the possibility that differences in their association pattern may change their functional contribution to vascular tone is largely unexplored. We probe this hypothesis using a model of essential hypertension (BPH mice; blood pressure high) and its normotensive control (BPN mice; blood pressure normal). First, non‐selective cationic currents through homo‐ and heterotetramers recorded from transfected Chinese hamster ovary cells indicated that TRPC currents were sensitive to the selective antagonist Pyr10 only when TRPC6 was present, whereas intracellular anti‐TRPC3 antibody selectively blocked TRPC3‐mediated currents. In mesenteric VSMCs, basal and agonist‐induced currents were more sensitive to Pyr3 and Pyr10 in BPN cells. Consistently, myography studies showed a larger Pyr3/10‐induced vasodilatation in BPN mesenteric arteries. mRNA and protein expression data supported changes in TRPC3 and TRPC6 proportions and assembly, with a higher TRPC3 channel contribution in BPH VSMCs that could favour cell depolarization. These differences in functional and pharmacological properties of TRPC3 and TRPC6 channels, depending on their assembly, could represent novel therapeutical opportunities.es
dc.format.mimetypeapplication/pdfes
dc.language.isoenges
dc.publisherThe Physiological Societyes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.classificationArterial smooth musclees
dc.subject.classificationMúsculo liso vasculares
dc.subject.classificationHypertensiones
dc.subject.classificationHipertensiónes
dc.titleDifferences in TRPC3 and TRPC6 channels assembly in mesenteric vascular smooth muscle cells in essential hypertensiones
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.holder© 2016 The Physiological Societyes
dc.identifier.doi10.1113/JP273327es
dc.relation.publisherversionhttps://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/JP273327es
dc.peerreviewedSIes
dc.description.projectInstituto de Salud Carlos III (project RD12/0042/0006)es
dc.description.projectPrograma Estatal de Investigación (project BFU2013-45867-R )es
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones


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