{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:30:48Z","timestamp":1793421048575,"version":"4.5.0"},"reference-count":52,"publisher":"Society for Neuroscience","issue":"5","license":[{"start":{"date-parts":[[2006,8,1]],"date-time":"2006-08-01T00:00:00Z","timestamp":1154390400000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2006,2,1]]},"abstract":"<jats:p>Ischemic episodes in the CNS cause significant disturbances in neuronal ionic homeostasis. To directly measure changes in intracellular Cl<jats:sup>\u2212<\/jats:sup>concentration ([Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>) during and after ischemia, we used Clomeleon, a novel ratiometric optical indicator for Cl<jats:sup>\u2212<\/jats:sup>. Hippocampal slices from adult transgenic mice expressing Clomeleon in hippocampal neurons were subjected to 8 min of oxygen-glucose deprivation (OGD) (an<jats:italic>in vitro<\/jats:italic>model for ischemia) and reoxygenated in the presence of glucose. This produced mild neuronal damage 3 h later that was prevented when the extracellular [Cl<jats:sup>\u2212<\/jats:sup>] was maintained at 10 m<jats:sc>m<\/jats:sc>during reoxygenation. OGD induced a transient decrease in fluorescence resonance energy transfer within Clomeleon, indicating an increase in [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>. During reoxygenation, there was a partial recovery in [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>, but [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>rose again 45 min later. To investigate sources of Cl<jats:sup>\u2212<\/jats:sup>accumulation, we examined the effects of Cl<jats:sup>\u2212<\/jats:sup>transport inhibitors on the rises in [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>during and after OGD. Bumetanide and furosemide, which inhibit Cl<jats:sup>\u2212<\/jats:sup>influx through the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup>cotransporter isoform-1 (NKCC-1) and efflux through the K<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup>cotransporter isoform-2, were unable to inhibit the first rise in [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>, yet entirely prevented the secondary rise in [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>during reoxygenation. In contrast, picrotoxin, which blocks the GABA-gated Cl<jats:sup>\u2212<\/jats:sup>channel, did not inhibit the secondary rise in [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>after OGD. [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>increases during reoxygenation were accompanied by an increase in phosphorylation of NKCC-1, an indication of increased NKCC-1 activity after OGD. We conclude that NKCC-1 plays an important role in OGD-induced Cl<jats:sup>\u2212<\/jats:sup>accumulation and subsequent neuronal damage.<\/jats:p>","DOI":"10.1523\/jneurosci.1421-05.2006","type":"journal-article","created":{"date-parts":[[2006,2,2]],"date-time":"2006-02-02T00:13:40Z","timestamp":1138839220000},"page":"1396-1406","source":"Crossref","is-referenced-by-count":117,"title":["The Chloride Transporter Na<sup>+<\/sup>-K<sup>+<\/sup>-Cl<sup>\u2212<\/sup>Cotransporter Isoform-1 Contributes to Intracellular Chloride Increases after<i>In Vitro<\/i>Ischemia"],"prefix":"10.1523","volume":"26","author":[{"given":"Brooks B.","family":"Pond","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Berglund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kuner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George J.","family":"Augustine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rochelle D.","family":"Schwartz-Bloom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2006,2,1]]},"reference":[{"key":"2023041303163895000_26.5.1396.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5539-03.2004"},{"key":"2023041303163895000_26.5.1396.2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017378"},{"key":"2023041303163895000_26.5.1396.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00091-4"},{"key":"2023041303163895000_26.5.1396.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-12-05061.2003"},{"key":"2023041303163895000_26.5.1396.5","unstructured":"Berglund K, Dunbar RL, Lee P, Feng G, Augustine GJ (2004) Imaging synaptic inhibition with Clomeleon, a genetically encoded chloride indicator. 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