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dc.contributor.authorParodi J.
dc.contributor.authorMontecinos-Oliva C.
dc.contributor.authorVaras R.
dc.contributor.authorAlfaro I.E.
dc.contributor.authorSerrano F.G.
dc.contributor.authorVaras-Godoy M.
dc.contributor.authorMuñoz F.J.
dc.contributor.authorCerpa W.
dc.contributor.authorGodoy J.A.
dc.contributor.authorInestrosa N.C.
dc.date.accessioned2020-09-02T22:25:21Z
dc.date.available2020-09-02T22:25:21Z
dc.date.issued2015
dc.identifier10.1016/j.mcn.2015.08.011
dc.identifier.citation68, , 314-322
dc.identifier.issn10447431
dc.identifier.urihttps://hdl.handle.net/20.500.12728/5749
dc.descriptionHippocampal synapses play a key role in memory and learning processes by inducing long-term potentiation and depression. Wnt signaling is essential in the development and maintenance of synapses via several mechanisms. We have previously found that Wnt5a induces the production of nitric oxide (NO), which modulates NMDA receptor expression in the postsynaptic regions of hippocampal neurons. Here, we report that Wnt5a selectively inhibits a voltage-gated K+ current (Kv current) and increases synaptic activity in hippocampal slices. Further supporting a specific role for Wnt5a, the soluble Frizzled receptor protein (sFRP-2; a functional Wnt antagonist) fully inhibits the effects of Wnt5a. We additionally show that these responses to Wnt5a are mediated by activation of a ROR2 receptor and increased NO production because they are suppressed by the shRNA-mediated knockdown of ROR2 and by 7-nitroindazole, a specific inhibitor of neuronal NOS. Together, our results show that Wnt5a increases NO production by acting on ROR2 receptors, which in turn inhibit Kv currents. These results reveal a novel mechanism by which Wnt5a may regulate the excitability of hippocampal neurons. © 2015 Elsevier Inc.
dc.language.isoen
dc.publisherAcademic Press Inc.
dc.subjectHippocampal neurons
dc.subjectK+ current
dc.subjectROR2 receptor
dc.subjectWnt5a
dc.subject7 nitroindazole
dc.subjectnitric oxide
dc.subjectreceptor tyrosine kinase like orphan receptor
dc.subjectvoltage gated potassium channel
dc.subjectWnt5a protein
dc.subject7-nitroindazole
dc.subjectenzyme inhibitor
dc.subjectindazole derivative
dc.subjectn(g) methylarginine
dc.subjectnitric oxide
dc.subjectpotassium
dc.subjectpotassium channel
dc.subjectreceptor tyrosine kinase like orphan receptor
dc.subjectRor2 protein, rat
dc.subjectWnt protein
dc.subjectWnt5a protein, rat
dc.subjectanimal cell
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectbrain cell culture
dc.subjectcontrolled study
dc.subjecthippocampal neuron
dc.subjecthippocampus potential
dc.subjectmale
dc.subjectnerve cell
dc.subjectnerve cell excitability
dc.subjectneuromodulation
dc.subjectnonhuman
dc.subjectpotassium current
dc.subjectpriority journal
dc.subjectprotein interaction
dc.subjectrat
dc.subjectregulatory mechanism
dc.subjectsynaptic transmission
dc.subjectWnt signaling pathway
dc.subjectanimal
dc.subjectC57BL mouse
dc.subjectcell culture
dc.subjectcytology
dc.subjectdrug effects
dc.subjectexcitatory postsynaptic potential
dc.subjectgenetic transduction
dc.subjectgenetics
dc.subjecthippocampus
dc.subjectin vitro study
dc.subjectmammalian embryo
dc.subjectmetabolism
dc.subjectmouse
dc.subjectnerve cell
dc.subjectphysiology
dc.subjectSprague Dawley rat
dc.subjectsynapse
dc.subjectAnimals
dc.subjectCells, Cultured
dc.subjectEmbryo, Mammalian
dc.subjectEnzyme Inhibitors
dc.subjectExcitatory Postsynaptic Potentials
dc.subjectHippocampus
dc.subjectIn Vitro Techniques
dc.subjectIndazoles
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectNeurons
dc.subjectNitric Oxide
dc.subjectomega-N-Methylarginine
dc.subjectPotassium
dc.subjectPotassium Channels
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectReceptor Tyrosine Kinase-like Orphan Receptors
dc.subjectSynapses
dc.subjectTransduction, Genetic
dc.subjectWnt Proteins
dc.titleWnt5a inhibits K+ currents in hippocampal synapses through nitric oxide production
dc.typeArticle


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