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Wnt5a inhibits K+ currents in hippocampal synapses through nitric oxide production
dc.contributor.author | Parodi J. | |
dc.contributor.author | Montecinos-Oliva C. | |
dc.contributor.author | Varas R. | |
dc.contributor.author | Alfaro I.E. | |
dc.contributor.author | Serrano F.G. | |
dc.contributor.author | Varas-Godoy M. | |
dc.contributor.author | Muñoz F.J. | |
dc.contributor.author | Cerpa W. | |
dc.contributor.author | Godoy J.A. | |
dc.contributor.author | Inestrosa N.C. | |
dc.date.accessioned | 2020-09-02T22:25:21Z | |
dc.date.available | 2020-09-02T22:25:21Z | |
dc.date.issued | 2015 | |
dc.identifier | 10.1016/j.mcn.2015.08.011 | |
dc.identifier.citation | 68, , 314-322 | |
dc.identifier.issn | 10447431 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12728/5749 | |
dc.description | Hippocampal 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.iso | en | |
dc.publisher | Academic Press Inc. | |
dc.subject | Hippocampal neurons | |
dc.subject | K+ current | |
dc.subject | ROR2 receptor | |
dc.subject | Wnt5a | |
dc.subject | 7 nitroindazole | |
dc.subject | nitric oxide | |
dc.subject | receptor tyrosine kinase like orphan receptor | |
dc.subject | voltage gated potassium channel | |
dc.subject | Wnt5a protein | |
dc.subject | 7-nitroindazole | |
dc.subject | enzyme inhibitor | |
dc.subject | indazole derivative | |
dc.subject | n(g) methylarginine | |
dc.subject | nitric oxide | |
dc.subject | potassium | |
dc.subject | potassium channel | |
dc.subject | receptor tyrosine kinase like orphan receptor | |
dc.subject | Ror2 protein, rat | |
dc.subject | Wnt protein | |
dc.subject | Wnt5a protein, rat | |
dc.subject | animal cell | |
dc.subject | animal tissue | |
dc.subject | Article | |
dc.subject | brain cell culture | |
dc.subject | controlled study | |
dc.subject | hippocampal neuron | |
dc.subject | hippocampus potential | |
dc.subject | male | |
dc.subject | nerve cell | |
dc.subject | nerve cell excitability | |
dc.subject | neuromodulation | |
dc.subject | nonhuman | |
dc.subject | potassium current | |
dc.subject | priority journal | |
dc.subject | protein interaction | |
dc.subject | rat | |
dc.subject | regulatory mechanism | |
dc.subject | synaptic transmission | |
dc.subject | Wnt signaling pathway | |
dc.subject | animal | |
dc.subject | C57BL mouse | |
dc.subject | cell culture | |
dc.subject | cytology | |
dc.subject | drug effects | |
dc.subject | excitatory postsynaptic potential | |
dc.subject | genetic transduction | |
dc.subject | genetics | |
dc.subject | hippocampus | |
dc.subject | in vitro study | |
dc.subject | mammalian embryo | |
dc.subject | metabolism | |
dc.subject | mouse | |
dc.subject | nerve cell | |
dc.subject | physiology | |
dc.subject | Sprague Dawley rat | |
dc.subject | synapse | |
dc.subject | Animals | |
dc.subject | Cells, Cultured | |
dc.subject | Embryo, Mammalian | |
dc.subject | Enzyme Inhibitors | |
dc.subject | Excitatory Postsynaptic Potentials | |
dc.subject | Hippocampus | |
dc.subject | In Vitro Techniques | |
dc.subject | Indazoles | |
dc.subject | Mice | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Neurons | |
dc.subject | Nitric Oxide | |
dc.subject | omega-N-Methylarginine | |
dc.subject | Potassium | |
dc.subject | Potassium Channels | |
dc.subject | Rats | |
dc.subject | Rats, Sprague-Dawley | |
dc.subject | Receptor Tyrosine Kinase-like Orphan Receptors | |
dc.subject | Synapses | |
dc.subject | Transduction, Genetic | |
dc.subject | Wnt Proteins | |
dc.title | Wnt5a inhibits K+ currents in hippocampal synapses through nitric oxide production | |
dc.type | Article |