{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T20:43:28Z","timestamp":1774471408231,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,2,17]],"date-time":"2009-02-17T00:00:00Z","timestamp":1234828800000},"content-version":"vor","delay-in-days":1569,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Voltage\u2010gated Na<jats:sup>+<\/jats:sup> channel blockers have been widely used as local anaesthetics and antiarrhythmic agents. It has recently been proposed that Na<jats:sup>+<\/jats:sup> channel agonists can be used as inotropic agents. Here, we report the identification of a natural substance that acts as a Na<jats:sup>+<\/jats:sup> channel agonist.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using the patch\u2010clamp technique in isolated rat ventricular myocytes, we investigated the electrophysiological effects of the substances isolated from the root extract of <jats:italic>Salvia miltiorrhiza<\/jats:italic>, which is known as \u2018Danshen\u2019 in Asian traditional medicine. By the intensive activity\u2010guided fractionation, we identified dimethyl lithospermate B (dmLSB) as the most active component, while LSB, which is the major component of the extract, showed negligible electrophysiological effect. Action potential duration (APD<jats:sub>90<\/jats:sub>) was increased by 20 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc> dmLSB from 58.8\u00b112.1 to 202.3\u00b19.5 ms. In spite of the prolonged APD, no early after\u2010depolarization (EAD) was observed.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>dmLSB had no noticeable effect on K<jats:sup>+<\/jats:sup> or Ca<jats:sup>2+<\/jats:sup> currents, but selectively affected Na<jats:sup>+<\/jats:sup> currents (<jats:italic>I<\/jats:italic><jats:sub>Na<\/jats:sub>). dmLSB slowed the inactivation kinetics of <jats:italic>I<\/jats:italic><jats:sub>Na<\/jats:sub> by increasing the proportion of slowly inactivating component without inducing any persistent <jats:italic>I<\/jats:italic><jats:sub>Na<\/jats:sub>. The relative amplitude of slow component compared to the peak fast <jats:italic>I<\/jats:italic><jats:sub>Na<\/jats:sub> was increased dose dependently by dmLSB (EC<jats:sub>50<\/jats:sub>=20 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>). Voltage dependence of inactivation was not affected by dmLSB, while voltage dependence of activation shifted by 5 mV to the depolarised direction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Since the APD prolongation by dmLSB did not provoke EAD, which is thought as a possible mechanism for the proarrhythmia seen in other Na<jats:sup>+<\/jats:sup> channel agonists, dmLSB might be an excellent candidate for a Na<jats:sup>+<\/jats:sup> channel agonist.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>143<\/jats:bold>, 765\u2013773. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705969\">10.1038\/sj.bjp.0705969<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705969","type":"journal-article","created":{"date-parts":[[2004,11,11]],"date-time":"2004-11-11T16:33:07Z","timestamp":1100190787000},"page":"765-773","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A novel Na<sup>+<\/sup> channel agonist, dimethyl lithospermate B, slows Na<sup>+<\/sup> current inactivation and increases action potential duration in isolated rat ventricular myocytes"],"prefix":"10.1111","volume":"143","author":[{"given":"Jin\u2010Young","family":"Yoon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung\u2010Hun","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyuncheol","family":"Oh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young\u2010Sup","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi Yong","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won\u2010Kyung","family":"Ho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suk\u2010Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.20.040180.000311"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(93)90129-Q"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215570"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp016916"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-3623(93)90176-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.37.1287"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000051660.82593.19"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705379"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.042218"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199805000-00006"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.19.228"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1996.tb00234.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3466.1995.tb00307.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1987.tb03197.x"},{"key":"e_1_2_7_16_1","first-page":"1067","article-title":"Actions of pyrethroid insecticides on sodium currents, action potentials, and contractile rhythm in isolated mammalian ventricular myocytes and perfused hearts","volume":"298","author":"SPENCER C.I.","year":"2001","journal-title":"J. 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