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Here, we show that hypoxia activates the Small Ubiquitin-like Modifier (SUMO) pathway in rat cerebellar granule neurons (CGN) and that SUMOylation of Na\n                    <jats:sub>V<\/jats:sub>\n                    1.2 channels increases\n                    <jats:italic>\n                      I\n                      <jats:sub>Na<\/jats:sub>\n                    <\/jats:italic>\n                    . The time-course for SUMOylation of single Na\n                    <jats:sub>V<\/jats:sub>\n                    1.2 channels at the cell surface and changes in\n                    <jats:italic>\n                      I\n                      <jats:sub>Na<\/jats:sub>\n                    <\/jats:italic>\n                    coincide, and both are prevented by mutation of Na\n                    <jats:sub>V<\/jats:sub>\n                    1.2-Lys38 or application of a deSUMOylating enzyme. Within 40 s, hypoxia-induced linkage of SUMO1 to the channels is complete, shifting the voltage-dependence of channel activation so that depolarizing steps evoke larger sodium currents. Given the recognized role of\n                    <jats:italic>\n                      I\n                      <jats:sub>Na<\/jats:sub>\n                    <\/jats:italic>\n                    in hypoxic brain damage, the SUMO pathway and Na\n                    <jats:sub>V<\/jats:sub>\n                    1.2 are identified as potential targets for neuroprotective interventions.\n                  <\/jats:p>","DOI":"10.7554\/elife.20054","type":"journal-article","created":{"date-parts":[[2016,12,28]],"date-time":"2016-12-28T08:00:22Z","timestamp":1482912022000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.20054","source":"Crossref","is-referenced-by-count":45,"title":["SUMOylation of NaV1.2 channels mediates the early response to acute hypoxia in central neurons"],"prefix":"10.7554","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1622-1655","authenticated-orcid":true,"given":"Leigh D","family":"Plant","sequence":"first","affiliation":[{"name":"Department of 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