{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:33:29Z","timestamp":1790645609517,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,12,29]],"date-time":"2016-12-29T00:00:00Z","timestamp":1482969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RIC, RD12\/0042\/0006, Red Heracles"],"award-info":[{"award-number":["RIC, RD12\/0042\/0006, Red Heracles"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Canonical transient receptor potential (TRPC)3 and TRPC6 channels of vascular smooth muscle cells (VSMCs) mediate stretch\u2010 or agonist\u2010induced cationic fluxes, contributing to membrane potential and vascular tone.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Native TRPC3\/C6 channels can form homo\u2010 or heterotetrameric complexes, which can hinder individual TRPC channel properties. The possibility that the differences in their association pattern may change their contribution to vascular tone in hypertension is unexplored.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Functional characterization of heterologously expressed channels showed that TRPC6\u2010containing complexes exhibited Pyr3\/Pyr10\u2010sensitive currents, whereas TRPC3\u2010mediated currents were blocked by anti\u2010TRPC3 antibodies.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>VSMCs from hypertensive (blood pressure high; BPH) mice have larger cationic basal currents insensitive to Pyr10 and sensitive to anti\u2010TRPC3 antibodies. Consistently, myography studies showed a larger Pyr3\/10\u2010induced vasodilatation in BPN (blood pressure normal) mesenteric arteries.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that the increased TRPC3 channel expression in BPH VSMCs leads to changes in TRPC3\/C6 heteromultimeric assembly, with a higher TRPC3 channel contribution favouring depolarization of hypertensive VSMCs.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Increased 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\u2010type Ca<jats:sup>2+<\/jats:sup> channel activity generates augmented Ca<jats:sup>2+<\/jats:sup> 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\u2010activated, non\u2010selective cationic channels contributing to stretch\u2010 or agonist\u2010induced depolarization. Conflicting information exists regarding changes in TRPC3\/TRPC6 functional expression in hypertension. However, although TRPC3\u2010TRPC6 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\u2010selective cationic currents through homo\u2010 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\u2010TRPC3 antibody selectively blocked TRPC3\u2010mediated currents. In mesenteric VSMCs, basal and agonist\u2010induced currents were more sensitive to Pyr3 and Pyr10 in BPN cells. Consistently, myography studies showed a larger Pyr3\/10\u2010induced 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.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp273327","type":"journal-article","created":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T13:52:15Z","timestamp":1479304335000},"page":"1497-1513","source":"Crossref","is-referenced-by-count":48,"title":["Differences in TRPC3 and TRPC6 channels assembly in mesenteric vascular smooth muscle cells in essential hypertension"],"prefix":"10.1113","volume":"595","author":[{"given":"In\u00e9s","family":"\u00c1lvarez\u2010Miguel","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Fisiolog\u00eda e Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM) Universidad de Valladolid y Consejo Superior de Investigaciones Cient\u00edficas (CSIC)  Valladolid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Cidad","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Fisiolog\u00eda e Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM) Universidad de Valladolid y Consejo Superior de Investigaciones Cient\u00edficas (CSIC)  Valladolid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8540-8117","authenticated-orcid":false,"given":"M. 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