{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:01:41Z","timestamp":1791104501879,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1993,8]]},"abstract":"<jats:p>The ionic current underlying the upstroke of axonal action potentials is carried by rapidly activating, voltage-dependent Na+ channels. Termination of the action potential is mediated in part by the rapid inactivation of these Na+ channels. We previously demonstrated that an influx of Na+ plays a critical role in the cascade leading to irreversible anoxic injury in central nervous system white matter. We speculated that a noninactivating Na+ conductance mediates this pathological Na+ influx and persists at depolarized membrane potentials as seen in anoxic axons. In the present study we measured the resting compound membrane potential of rat optic nerves using a modified \"grease-gap\" technique. Application of tetrodotoxin (2 microM) to resting nerves ([K+]o = 3 mM) or to nerves depolarized by 15 or 40 mM K+ resulted in hyperpolarizing shifts of membrane potential. We interpret these shifts as evidence for a persistent, noninactivating Na+ conductance. This conductance is present at rest and persists in nerves depolarized sufficiently to abolish classical transient Na+ currents. PK\/PNa ratios were estimated at 35.5, 23.2, and 88 in 3 mM, 15 mM, and 40 mM K+, respectively. We suggest that this noninactivating Na+ conductance may provide an inward pathway for Na+ ions, necessary for the operation of Na+, K(+)-ATPase. Under pathological conditions, such as anoxia, this conductance is the likely route of Na+ influx, which causes damaging Ca2+ entry through reverse operation of the Na(+)-Ca2+ exchanger. The presence of this conductance in white matter axons may provide a therapeutic opportunity for diseases such as stroke and spinal cord injury.<\/jats:p>","DOI":"10.1073\/pnas.90.15.6976","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:28:31Z","timestamp":1149064111000},"page":"6976-6980","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":174,"title":["Noninactivating, tetrodotoxin-sensitive Na+ conductance in rat optic nerve axons."],"prefix":"10.1073","volume":"90","author":[{"given":"P K","family":"Stys","sequence":"first","affiliation":[{"name":"Department of Neurology, Yale School of Medicine, New Haven, CT 06510."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Sontheimer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine, New Haven, CT 06510."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B R","family":"Ransom","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine, New Haven, CT 06510."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S G","family":"Waxman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine, New Haven, CT 06510."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1993,8]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.90.15.6976","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:27:13Z","timestamp":1649856433000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.90.15.6976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,8]]},"references-count":0,"journal-issue":{"issue":"15","published-print":{"date-parts":[[1993,8]]}},"alternative-id":["10.1073\/pnas.90.15.6976"],"URL":"https:\/\/doi.org\/10.1073\/pnas.90.15.6976","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,8]]},"assertion":[{"value":"1993-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}