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dc.contributor.authorWatanabe, H.
dc.contributor.authorDavis, J.B.
dc.contributor.authorSmart, D.
dc.contributor.authorJerman, J.C.
dc.contributor.authorSmith, G.D.
dc.contributor.authorHayes, P.
dc.contributor.authorVriens, J.
dc.contributor.authorCairns, W.
dc.contributor.authorWissenbach, U.
dc.contributor.authorPrenen, J.
dc.contributor.authorFlockerzi, G.D.
dc.contributor.authorDroogmans, G.
dc.contributor.authorBenham, C.D.
dc.contributor.authorNilius, B.
dc.identifier.citationWatanabe , H , Davis , J B , Smart , D , Jerman , J C , Smith , G D , Hayes , P , Vriens , J , Cairns , W , Wissenbach , U , Prenen , J , Flockerzi , G D , Droogmans , G , Benham , C D & Nilius , B 2002 , ' Activation of TRPV4 channels (hVRL-2/mTrp12) by phorbol derivatives ' , Journal of Biological Chemistry , vol. 277 , no. 16 , pp. 13569-13577 .
dc.identifier.otherPURE: 124627
dc.identifier.otherPURE UUID: d0946f97-d7eb-4356-be9a-48ed42df9c96
dc.identifier.otherdspace: 2299/3508
dc.identifier.otherScopus: 0037134482
dc.descriptionThe original article can be found at: Copyright by The American Society for Biochemistry and Molecular Biology. DOI: 10.1074/jbc.M200062200 [Full text of this article is not available in the UHRA]
dc.description.abstractWe have studied activation by phorbol derivatives of TRPV4 channels, the human VRL-2, and murine TRP12 channels, which are highly homologous to the human VR-OAC, and the human and murine OTRPC4 channel. 4α-Phorbol 12,13-didecanoate (4α-PDD) induced an increase in intracellular Ca2+ concentration, [Ca2+]i, in 1321N1 cells stably transfected with human VRL-2 (hVRL-2.1321N1) or HEK-293 cells transiently transfected with murine TRP12, but not in nontransfected or mock-transfected cells. Concomitantly with the increase in [Ca2+]i, 4α-PDD activated an outwardly rectifying cation channel with an Eisenman IV permeation sequence for monovalent cations that is Ca2+-permeable withP Ca/P Na = 5.8. Phorbol 12-myristate 13-acetate also induced an increase in [Ca2+]i but was ∼50 times less effective than 4α-PDD. EC50 for Ca2+ increase and current activation was nearly identical (pEC50 ∼ 6.7). Similar effects were observed in freshly isolated mouse aorta endothelial cells which express TRP12 endogenously. By using 4α-PDD as a tool to stimulate TRP12, we showed that activation of this channel is modulated by [Ca2+]i; an increase in [Ca2+]i inhibits the channel with an IC50 of 406 nm. Ruthenium Red at a concentration of 1 μm completely blocks inward currents at −80 mV but has a smaller effect on outward currents likely indicating a voltage dependent channel block. We concluded that the phorbol derivatives activate TRPV4 (VR-OAC, VRL-2, OTRPC4, TRP12) independently from protein kinase C, in a manner consistent with direct agonist gating of the channel.en
dc.relation.ispartofJournal of Biological Chemistry
dc.titleActivation of TRPV4 channels (hVRL-2/mTrp12) by phorbol derivativesen
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.description.statusPeer reviewed
rioxxterms.typeJournal Article/Review

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