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K<jats:sup>+<\/jats:sup> currents in OPCs are developmentally regulated during differentiation. However, the mechanisms regulating these currents at different stages of oligodendrocyte lineage are poorly understood. Here we show that, in cultured primary OPCs, the purinergic G\u2010protein coupled receptor GPR17, that has recently emerged as a key player in oligodendrogliogenesis, crucially regulates K<jats:sup>+<\/jats:sup> currents. Specifically, receptor stimulation by its agonist UDP\u2010glucose enhances delayed rectifier K<jats:sup>+<\/jats:sup> currents without affecting transient K<jats:sup>+<\/jats:sup> conductances. This effect was observed in a subpopulation of OPCs and immature pre\u2010OLGs whereas it was absent in mature OLGs, in line with GPR17 expression, that peaks at intermediate phases of oligodendrocyte differentiation and is thereafter downregulated to allow terminal maturation. The effect of UDP\u2010glucose on K<jats:sup>+<\/jats:sup> currents is concentration\u2010dependent, blocked by the GPR17 antagonists MRS2179 and cangrelor, and sensitive to the K<jats:sup>+<\/jats:sup> channel blocker tetraethyl\u2010ammonium, which also inhibits oligodendrocyte maturation. We propose that stimulation of K<jats:sup>+<\/jats:sup> currents is responsible for GPR17\u2010induced oligodendrocyte differentiation. Moreover, we demonstrate, for the first time, that GPR17 activation stimulates OPC migration, suggesting an important role for this receptor after brain injury. Our data indicate that modulation of GPR17 may represent a strategy to potentiate the post\u2010traumatic response of OPCs under demyelinating conditions, such as multiple sclerosis, stroke, and brain trauma.<\/jats:p>","DOI":"10.1002\/glia.22506","type":"journal-article","created":{"date-parts":[[2013,5,2]],"date-time":"2013-05-02T18:49:19Z","timestamp":1367520559000},"page":"1155-1171","source":"Crossref","is-referenced-by-count":60,"title":["UDP\u2010glucose enhances outward K<sup>+<\/sup> currents necessary for cell differentiation and stimulates cell migration by activating the GPR17 receptor in oligodendrocyte precursors"],"prefix":"10.1002","volume":"61","author":[{"given":"Elisabetta","family":"Coppi","sequence":"first","affiliation":[{"name":"Division of Pharmacology and Toxicology Department of Neuroscience Psychology, Drug Research and Child Health (NeuroFarBa) University of Florence Viale Pieraccini, 6 50139 Florence 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