{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:25:24Z","timestamp":1760783124216},"reference-count":67,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:p>Learning and memory depend on neuronal alterations induced by electrical activity. Most examples of activity-dependent plasticity, as well as adaptive responses to neuronal injury, have been linked explicitly or implicitly to induction by Ca<jats:sup>2+<\/jats:sup>signals produced by depolarization. Indeed, transient Ca<jats:sup>2+<\/jats:sup>signals are commonly assumed to be the only effective transducers of depolarization into adaptive neuronal responses. Nevertheless, Ca<jats:sup>2+<\/jats:sup>-independent depolarization-induced signals might also trigger plastic changes. Establishing the existence of such signals is a challenge because procedures that eliminate Ca<jats:sup>2+<\/jats:sup>transients also impair neuronal viability and tolerance to cellular stress. We have taken advantage of nociceptive sensory neurons in the marine snail Aplysia, which exhibit unusual tolerance to extreme reduction of extracellular and intracellular free Ca<jats:sup>2+<\/jats:sup>levels. The axons of these neurons exhibit a depolarization-induced memory-like hyperexcitability that lasts a day or longer and depends on local protein synthesis for induction. Here we show that transient localized depolarization of these axons in an excised nerve\u2013ganglion preparation or in dissociated cell culture can induce short- and intermediate-term axonal hyperexcitability as well as long-term protein synthesis\u2013dependent hyperexcitability under conditions in which Ca<jats:sup>2+<\/jats:sup>entry is prevented (by bathing in nominally Ca<jats:sup>2+<\/jats:sup>-free solutions containing EGTA) and detectable Ca<jats:sup>2+<\/jats:sup>transients are eliminated (by adding BAPTA-AM). Disruption of Ca<jats:sup>2+<\/jats:sup>release from intracellular stores by pretreatment with thapsigargin also failed to affect induction of axonal hyperexcitability. These findings suggest that unrecognized Ca<jats:sup>2+<\/jats:sup>-independent signals exist that can transduce intense depolarization into adaptive cellular responses during neuronal injury, prolonged high-frequency activity, or other sustained depolarizing events.<\/jats:p>","DOI":"10.1152\/jn.91012.2008","type":"journal-article","created":{"date-parts":[[2009,1,15]],"date-time":"2009-01-15T03:36:29Z","timestamp":1231990589000},"page":"1351-1360","source":"Crossref","is-referenced-by-count":9,"title":["Long-Lasting Hyperexcitability Induced by Depolarization in the Absence of Detectable Ca<sup>2+<\/sup>Signals"],"prefix":"10.1152","volume":"101","author":[{"given":"Kumud K.","family":"Kunjilwar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harvey M.","family":"Fishman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario J.","family":"Englot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger G.","family":"O'Neil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgar T.","family":"Walters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-09-02655.1991"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2005.12.008"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1038\/nature05259"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1993.69.1.151"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(92)90035-D"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(93)90009-G"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3520-07.2007"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1126\/science.2903551"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2093"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81653-0"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2007.05.001"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00026-5"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01089.2006"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1198"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1101\/lm.984508"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(83)90100-8"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1038\/nn1568"},{"key":"R18","doi-asserted-by":"crossref","unstructured":"Fishman HM, Bittner GD.Vesicle-mediated restoration of a plasmalemmal barrier in severed axons.News Physiol Sci18: 115\u2013118, 2003.","DOI":"10.1152\/nips.01429.2002"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1016\/S0143416002001999"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(07)00017-9"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1982.sp014227"},{"key":"R22","doi-asserted-by":"crossref","unstructured":"Grynkiewicz G, Poenie M, Tsien RY.A new generation of Ca2+indicators with greatly improved fluorescence properties.J Biol Chem260: 3440\u20133450, 1985.","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1126\/science.6294833"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505909103"},{"key":"R25","unstructured":"Hille B.Ion Channels of Excitable Membranes(3rd ed.). 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