{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:41:31Z","timestamp":1791160891848,"version":"4.1.0"},"reference-count":55,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2003,3,1]]},"abstract":"<jats:p>To clarify the changes that occur in \u03b3-aminobutyric acid type A (GABA<jats:sub>A<\/jats:sub>) receptor-mediated effects and contribute to alterations in the network activities after neuronal injury, we studied intracellular Ca<jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) dynamics in a rat facial-nerve-transection model. In facial motoneurons, an elevation of the resting [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, GABA-mediated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>transients, enhancement of the glutamate-evoked [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>increases, and spontaneous [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>oscillations were induced by axotomy. All these axotomy-induced modifications were abolished by the GABA<jats:sub>A<\/jats:sub>-receptor antagonist bicuculline and N-methyl-d-aspartate (NMDA)-receptor antagonistd(\u2212)-2-amino-5-phosphonopentanoic acid. A downregulation of K<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup>cotransporter (KCC2) mRNA, an increase in intracellular Cl<jats:sup>\u2212<\/jats:sup>concentration ([Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>), and transformation of GABAergic hyperpolarization to depolarization were also induced by axotomy. We suggest that in axotomized neurons KCC2 downregulation impairs Cl<jats:sup>\u2212<\/jats:sup>homeostasis and makes GABA act depolarizing, resulting in endogenous GABA inducing [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>oscillations via facilitation of NMDA-receptor activation. Such GABA<jats:sub>A<\/jats:sub>-receptor-mediated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>oscillations may play a role in neural survival and regeneration.<\/jats:p>","DOI":"10.1152\/jn.00721.2002","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T06:01:10Z","timestamp":1149055270000},"page":"1353-1362","source":"Crossref","is-referenced-by-count":113,"title":["Induction of NMDA and GABA<sub>A<\/sub>Receptor-Mediated Ca<sup>2+<\/sup>Oscillations With KCC2 mRNA Downregulation in Injured Facial Motoneurons"],"prefix":"10.1152","volume":"89","author":[{"given":"Hiroki","family":"Toyoda","sequence":"first","affiliation":[{"name":"Departments of Physiology,"},{"name":"Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Ohno","sequence":"additional","affiliation":[{"name":"Anatomy, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Biological Information Processing, Graduate School of Electronic Science and Technology, Shizuoka University, Hamamatsu, Shizuoka 432-8011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Departments of Physiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihito","family":"Okabe","sequence":"additional","affiliation":[{"name":"Departments of Physiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohji","family":"Sato","sequence":"additional","affiliation":[{"name":"Anatomy, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuo","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Departments of Physiology,"},{"name":"Department of Biological Information Processing, Graduate School of Electronic Science and Technology, Shizuoka University, Hamamatsu, Shizuoka 432-8011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8097060"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90505-F"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-05-01808.1996"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nrn920"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017762"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(88)90275-3"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(97)01147-8"},{"key":"B8","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1242\/dev.121.8.2327","volume":"121","author":"Berninger B","year":"1995","journal-title":"Development"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1021\/bi00246a001"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/BF00325030"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021505"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/0736-5748(90)90080-L"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-21-08069.2000"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020649"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80433-X"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(92)90103-F"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.79.1.439"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(98)00099-6"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(99)00553-9"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00341-5"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/74823"},{"key":"B22","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","volume":"260","author":"Grynkiewicz G","year":"1985","journal-title":"J Biol Chem"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-12-04695.1999"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(94)90049-3"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-08-02843.1999"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00149-X"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021900"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80265-2"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020882"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90008-X"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(19990615)39:4<558::AID-NEU9>3.0.CO;2-5"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1991.65.2.247"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(98)00112-6"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-11-04412.2002"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)91562-S"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-07-05065.1995"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19960819)372:2<167::AID-CNE1>3.0.CO;2-1"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-20-06414.1996"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.27.16245"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(19971120)33:6<781::AID-NEU6>3.0.CO;2-5"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/16697"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/BF00247935"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(95)00075-5"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020973"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1991.261.5.C906"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1981.tb00089.x"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890020104"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/glia.440070112"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1999.81.4.1939"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-13-04283.1996"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092380211"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/318558a0"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050160"},{"key":"B54","first-page":"148.4","volume":"28","author":"Yamada J","year":"2002","journal-title":"Soc Neurosci Abstr"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90243-S"}],"container-title":["Journal of Neurophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/jn.00721.2002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T21:54:02Z","timestamp":1627422842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/jn.00721.2002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,3,1]]},"references-count":55,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2003,3,1]]}},"alternative-id":["10.1152\/jn.00721.2002"],"URL":"https:\/\/doi.org\/10.1152\/jn.00721.2002","relation":{},"ISSN":["0022-3077","1522-1598"],"issn-type":[{"value":"0022-3077","type":"print"},{"value":"1522-1598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,3,1]]}}}