{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T04:50:55Z","timestamp":1744087855145},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,12,11]],"date-time":"2012-12-11T00:00:00Z","timestamp":1355184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Lamotrigine is a neuroprotective agent that is used clinically for the treatment of seizures and neuropathic pain. A significant volume of literature has reported that lamotrigine exerts analgesic effect by blocking Ca<jats:sup>2+<\/jats:sup> channels. However, little is known regarding the effect of lamotrigine on the intracellular Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>). The aim of this study was to determine whether lamotrigine modulates [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in sensory neurones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lamotrigine\u2010induced changes in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> were measured in mouse dorsal root ganglion (<jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content>) neurones using the Ca<jats:sup>2+<\/jats:sup>\u2010sensitive fluorescent indicator Fluo 3\u2010<jats:styled-content style=\"fixed-case\">AM<\/jats:styled-content> and a confocal laser scanning microscope. Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent kinase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> (Ca<jats:styled-content style=\"fixed-case\">MKII<\/jats:styled-content>) activation was assessed by the fluorescence intensity using immunocytochemical procedures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with 1, 10, 30 or 100\u00a0\u03bc<jats:sc>m<\/jats:sc> lamotrigine transiently increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in <jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content> neurones in a dose\u2010dependent manner. Treatment with 100\u00a0\u03bc<jats:sc>m<\/jats:sc> lamotrigine induced a significant (threefold) increase in the Ca<jats:sup>2+<\/jats:sup> peak in the presence or absence of extracellular Ca<jats:sup>2+<\/jats:sup>. The lamotrigine\u2010induced Ca<jats:sup>2+<\/jats:sup> increase was abolished or decreased by the treatment with a specific <jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content> inhibitor (U73122), <jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content>3R antagonist (xestospongin C) or RyR antagonist (dantrolene). In some cells, treatment with 100\u00a0\u03bc<jats:sc>m<\/jats:sc> lamotrigine caused a transient Ca<jats:sup>2+<\/jats:sup> increase, and the Ca<jats:sup>2+<\/jats:sup> levels quickly fell to below the basal Ca<jats:sup>2+<\/jats:sup> level observed prior to lamotrigine application. The decrease in basal Ca<jats:sup>2+<\/jats:sup> levels was blocked by the treatment with a Ca<jats:styled-content style=\"fixed-case\">MKII<\/jats:styled-content> inhibitor (<jats:styled-content style=\"fixed-case\">KN<\/jats:styled-content>93). Immunocytochemical analysis indicated that lamotrigine treatment increased the expression of phosphorylated Ca<jats:styled-content style=\"fixed-case\">MKII<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">DRG<\/jats:styled-content> neurones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Treatment with lamotrigine increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> apparently as a result of Ca<jats:sup>2+<\/jats:sup> release from intracellular stores and Ca<jats:styled-content style=\"fixed-case\">MKII<\/jats:styled-content> activity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12034","type":"journal-article","created":{"date-parts":[[2012,12,11]],"date-time":"2012-12-11T11:43:11Z","timestamp":1355226191000},"page":"397-404","source":"Crossref","is-referenced-by-count":6,"title":["Lamotrigine increases intracellular Ca<sup>2+<\/sup> levels and Ca<sup>2+<\/sup>\/calmodulin\u2010dependent kinase <scp>II<\/scp> activation in mouse dorsal root ganglion neurones"],"prefix":"10.1111","volume":"207","author":[{"given":"E. S.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine and Institute of Health Sciences Gyeongsang National University School of Medicine Jinju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. H.","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences Gyeongsang National University School of Medicine Jinju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.\u2010J.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences Gyeongsang National University School of Medicine Jinju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.\u2010T.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences Gyeongsang National University School of Medicine Jinju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.\u2010W.","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences Gyeongsang National University School of Medicine Jinju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.\u2010J.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences Gyeongsang National University School of Medicine Jinju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.\u2010M.","family":"Tak","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences Gyeongsang National University School of Medicine Jinju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences Gyeongsang National University School of Medicine Jinju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Institute of Health Sciences Gyeongsang National University School of Medicine Jinju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,12,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.323915"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005335"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ftd.0000245779.64080.30"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.152165"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-009-0686-7"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2007.00839.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00043.2007"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.12.013"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.anes.0000267538.72900.68"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7716515"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000026528"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(01)00145-1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2008.12.5.245"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2006.01.005"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/02688690701219175"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.06.083"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.01.008"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2011.05634.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22209"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020904"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70059-4"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200607000-00026"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-005-2146-1"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-3147.83577"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4160(94)90076-0"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-7-20"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.07.014"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp021078"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/eujp.2001.0315"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1094-z"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(96)00265-8"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199904260-00019"},{"key":"e_1_2_7_34_1","first-page":"421","article-title":"Lamotrigine in the treatment of pain syndromes and neuropathic pain","volume":"109","author":"Titlic M.","year":"2008","journal-title":"Bratisl Lek Listy"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-7-30"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.0115o.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00540-010-1068-1"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-977X(96)00384-7"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-2-21"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.1342"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2002.51401.x"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapha.12034","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.12034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T08:52:50Z","timestamp":1698655970000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.12034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,11]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,2]]}},"alternative-id":["10.1111\/apha.12034"],"URL":"https:\/\/doi.org\/10.1111\/apha.12034","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,11]]}}}