{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:57:52Z","timestamp":1768093072014,"version":"3.49.0"},"reference-count":87,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,11,23]],"date-time":"2013-11-23T00:00:00Z","timestamp":1385164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:p>Glycine GlyT2 transporters are localized on glycine\u2010storing nerve endings. Their main function is to accumulate glycine to replenish synaptic vesicles. Glycine was reported to be costored with \u03b3\u2010aminobutyric acid (GABA) in cerebellar interneurons that may coexpress glycine and GABA transporters, and this is confirmed here by confocal microscopy analysis showing coexpression of GAT1 and GlyT2 transporters on microtubule\u2010associated protein\u20102\u2010positive synaptosomes. It was found that GABA uptake elicited glycine release from cerebellar nerve endings by various mechanisms. We investigated whether and by what mechanisms activation of glycine transporters could mediate release of GABA. Nerve endings purified from cerebellum were prelabeled with [<jats:sup>3<\/jats:sup>H]GABA and exposed to glycine. Glycine stimulated [<jats:sup>3<\/jats:sup>H]GABA release in a concentration\u2010dependent manner. The glycine effect was insensitive to strychnine or to 5,7\u2010dichlorokynurenate but it was abolished when GlyT2 transporters were blocked. About 20% of the evoked release was dependent on external Ca<jats:sup>2+<\/jats:sup>entered by reversal of plasmalemmal Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup>exchangers. A significant portion of the GlyT2\u2010mediated release of [<jats:sup>3<\/jats:sup>H]GABA (about 50% of the external Ca<jats:sup>2+<\/jats:sup>\u2010independent release) occurred by reversal of GABA GAT1 transporters. Na<jats:sup>+<\/jats:sup>ions, reaching the cytosol during glycine uptake through GlyT2, activated mitochondrial Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup>exchangers, causing an increase in cytosolic Ca<jats:sup>2+<\/jats:sup>, which in turn triggered a Ca<jats:sup>2+<\/jats:sup>\u2010induced Ca<jats:sup>2+<\/jats:sup>release process at inositoltrisphosphate receptors. Finally, the increased availability of Ca<jats:sup>2+<\/jats:sup>in the cytosol allowed the opening of anion channels permeable to GABA. In conclusion, GlyT2 transporters not only take up glycine to replenish synaptic vesicles but can also mediate release of GABA by reversal of GAT1 and permeation through anion channels. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23321","type":"journal-article","created":{"date-parts":[[2013,11,25]],"date-time":"2013-11-25T08:57:50Z","timestamp":1385369870000},"page":"398-408","source":"Crossref","is-referenced-by-count":15,"title":["A new function for glycine GlyT2 transporters: Stimulation of \u03b3\u2010aminobutyric acid release from cerebellar nerve terminals through GAT1 transporter reversal and Ca<sup>2+<\/sup>\u2010dependent anion channels"],"prefix":"10.1002","volume":"92","author":[{"given":"Marco","family":"Milanese","sequence":"first","affiliation":[{"name":"Department of Pharmacy Pharmacology and Toxicology Section, University of Genoa Genoa Italy"},{"name":"Center of Excellence for Biomedical Research University of Genoa Genoa 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