{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T11:24:25Z","timestamp":1789212265676,"version":"build-2803163510"},"reference-count":74,"publisher":"Society for Neuroscience","issue":"43","license":[{"start":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T00:00:00Z","timestamp":1146009600000},"content-version":"vor","delay-in-days":182,"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":[[2005,10,26]]},"abstract":"<jats:p>The contribution of intracellular stores to axonal Ca<jats:sup>2+<\/jats:sup>overload during chemical ischemia<jats:italic>in vitro<\/jats:italic>was examined by confocal microscopy. Ca<jats:sup>2+<\/jats:sup>accumulation was measured by fluo-4 dextran (low-affinity dye,<jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub>\u2248 4 \u03bc<jats:sc>m<\/jats:sc>) or by Oregon Green 488 BAPTA-1 dextran (highaffinity dye,<jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub>\u2248 450 n<jats:sc>m<\/jats:sc>). Axonal Na<jats:sup>+<\/jats:sup>was measured using CoroNa Green. Ischemia in CSF containing 2 m<jats:sc>m<\/jats:sc>Ca<jats:sup>2+<\/jats:sup>caused an \u223c3.5-fold increase in fluo-4 emission after 30 min, indicating a large axonal Ca<jats:sup>2+<\/jats:sup>rise well into the micromolar range. Axonal Na<jats:sup>+<\/jats:sup>accumulation was enhanced by veratridine and reduced, but not abolished, by TTX. Ischemia in Ca<jats:sup>2+<\/jats:sup>-free (plus BAPTA) perfusate resulted in a smaller but consistent Ca<jats:sup>2+<\/jats:sup>increase monitored by Oregon Green 488 BAPTA-1, indicating release from intracellular sources. This release was eliminated in large part when Na<jats:sup>+<\/jats:sup>influx was reduced by replacement with<jats:italic>N<\/jats:italic>-methyl-<jats:sc>d<\/jats:sc>-glucamine (NMDG<jats:sup>+<\/jats:sup>; even in depolarizing high K<jats:sup>+<\/jats:sup>perfusate), Li<jats:sup>+<\/jats:sup>, or by the application of TTX and significantly increased by veratridine. Intracellular release also was reduced significantly by neomycin or 1-(6-[(17\u03b2-methoxyestra-1,3,5 [10]-trien-17-yl) amino] hexyl)-<jats:sup>1<\/jats:sup><jats:italic>H<\/jats:italic>-pyrrole-2,5-dione (\u00a0U73122) (phospholipase C inhibitors), heparin [inositol trisphosphate (IP<jats:sub>3<\/jats:sub>) receptor blocker], or 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(<jats:sup>3<\/jats:sup><jats:italic>H<\/jats:italic>)-one (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"CGP37157\" ext-link-type=\"genpept\" xlink:type=\"simple\">CGP37157<\/jats:ext-link>; mitochondrial Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup>exchange inhibitor) as well as ryanodine. Combining<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"CGP37157\" ext-link-type=\"genpept\" xlink:type=\"simple\">CGP37157<\/jats:ext-link>with \u00a0U73122 or heparin decreased the response more than either agent alone and significantly improved electrophysiological recovery. Our conclusion is that intra-axonal Ca<jats:sup>2+<\/jats:sup>release during ischemia in rat optic nerve is mainly dependent on Na<jats:sup>+<\/jats:sup>influx. This Na<jats:sup>+<\/jats:sup>accumulation stimulates three distinct intra-axonal sources of Ca<jats:sup>2+<\/jats:sup>: (1) the mitochondrial Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup>exchanger driven in the Na<jats:sup>+<\/jats:sup>import\/Ca<jats:sup>2+<\/jats:sup>export mode, (2) positive modulation of ryanodine receptors, and (3) promotion of IP<jats:sub>3<\/jats:sub>generation by phospholipase C.<\/jats:p>","DOI":"10.1523\/jneurosci.2003-05.2005","type":"journal-article","created":{"date-parts":[[2005,10,26]],"date-time":"2005-10-26T19:23:29Z","timestamp":1130354609000},"page":"9960-9967","source":"Crossref","is-referenced-by-count":80,"title":["Na<sup>+<\/sup>-Dependent Sources of Intra-Axonal Ca<sup>2+<\/sup>Release in Rat Optic Nerve during<i>In Vitro<\/i>Chemical Ischemia"],"prefix":"10.1523","volume":"25","author":[{"given":"Maria 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