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In A23187\u2010 or TG\u2010treated cells, veratridine\u2010induced <jats:sup>22<\/jats:sup>Na<jats:sup>+<\/jats:sup> influx was reduced (with no change in veratridine EC<jats:sub>50<\/jats:sub> value) while it was enhanced by \u03b1\u2010scorpion venom, \u03b2\u2010scorpion venom, or <jats:italic>Ptychodiscus brevis<\/jats:italic> toxin\u20103, like in nontreated cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The A23187\u2010 or TG\u2010induced decrease of [<jats:sup>3<\/jats:sup>H]\u2010STX binding was diminished by BAPTA\u2010AM. EGTA also inhibited the decreasing effect of A23187. A23187 caused a rapid, monophasic and persistent increase in intracellular concentration of Ca<jats:sup>2+<\/jats:sup> ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) to a greater extent than that observed with TG. 2,5\u2010Di\u2010(t\u2010butyl)\u20101,4\u2010benzohydroquinone (DBHQ) (an inhibitor of SERCA) produced only a rapid monophasic increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, without any effect on [<jats:sup>3<\/jats:sup>H]\u2010STX binding.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Reduction in [<jats:sup>3<\/jats:sup>H]\u2010STX binding capacity induced by A23187 or TG was attenuated by G\u00f66976 (an inhibitor of conventional protein kinase C) or calpastatin peptide (an inhibitor of calpain). When the internalization rate of cell surface Na<jats:sup>+<\/jats:sup> channels was measured in the presence of brefeldin A (an inhibitor of vesicular exit from the <jats:italic>trans<\/jats:italic>\u2010Golgi network), A23187 or TG accelerated the reduction of [<jats:sup>3<\/jats:sup>H]\u2010STX binding capacity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Six hours treatment with A23187 lowered Na<jats:sup>+<\/jats:sup> channel \u03b1\u2010 and \u03b2<jats:sub>1<\/jats:sub>\u2010subunit mRNA levels, whereas TG had no effect.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results suggest that elevation of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> caused by A23187, TG or DBHQ exerted differential effects on down\u2010regulation of cell surface functional Na<jats:sup>+<\/jats:sup> channels and Na<jats:sup>+<\/jats:sup> channel subunit mRNA levels.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>132<\/jats:bold>, 1455\u20131466; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703960\">10.1038\/sj.bjp.0703960<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703960","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:33:04Z","timestamp":1106947984000},"page":"1455-1466","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Heterogeneous increases of cytoplasmic calcium: distinct effects on down\u2010regulation of cell surface sodium channels and sodium channel subunit mRNA levels"],"prefix":"10.1111","volume":"132","author":[{"given":"Seiji","family":"Shiraishi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izumi","family":"Shibuya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhito","family":"Uezono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Yokoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumiko","family":"Toyohira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuichi","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiko","family":"Yanagita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideyuki","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiko","family":"Wada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.144.2.241"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017849"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.1993.tb00216.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90708-7"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8378"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.1016\/S0021-9258(17)33092-2","article-title":"Purification of a toxic protein from scorpion venom which activates the action potential Na+ ionophore","volume":"251","author":"CATTERALL W.A.","year":"1976","journal-title":"J. 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