{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:48:48Z","timestamp":1792111728373,"version":"4.4.0"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":3378,"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":[[1999,11]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The effects of 4\u2010Chloro\u2010m\u2010Cresol (4\u2010CmC) were examined on heterologously expressed wild type (WT), Paramyotonia Congenita (R1448H) and Hyperkalemic Periodic Paralysis (M1360V) mutant \u03b1\u2010subunits of human muscle sodium channels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Block of rested sodium channels caused by 4\u2010CmC was concentration\u2010dependent with an ECR<jats:sub>50<\/jats:sub> of 0.40\u2003m<jats:sc>M<\/jats:sc> in WT, 0.45\u2003m<jats:sc>M<\/jats:sc> in R1448H and 0.49\u2003m<jats:sc>M<\/jats:sc> in M1360V.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inactivation significantly promoted 4\u2010CmC\u2010induced sodium channel block in all clones indicated by 4\u2010CmC\u2010induced shifts of steady\u2010state availability curves, reflecting a higher proportion of channel block at depolarized membrane potentials. Channel block was almost complete (&gt;90%) at concentrations close to the ECR<jats:sub>50<\/jats:sub> (0.5\u2003m<jats:sc>M<\/jats:sc>) on application of an inactivating prepulse before the test pulse.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>4\u2010CmC accelerated the current decay following depolarization and prolonged recovery from inactivation in all clones. Of these, R1448H, the mutant which displayed severely impaired inactivation in the controls, responded to 4\u2010CmC with the most pronounced acceleration of inactivation. Control experiments revealed enhanced recovery from inactivation in the mutants, which was restored to normal in 0.1\u2003m<jats:sc>M<\/jats:sc> 4\u2010CmC.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>4\u2010CmC induced no additional frequency\u2010dependent block.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our results clearly demonstrate that 4\u2010CmC is as effective as lidocaine (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#b6\">Fan <jats:italic>et al<\/jats:italic>., 1996<\/jats:ext-link>) in blocking muscle sodium channels. Low concentrations of the compound (ECR<jats:sub>50<\/jats:sub>) were able to restore pathologically accelerated recovery from inactivation and impaired inactivation in the mutants to the WT value.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>128<\/jats:bold>, 1259\u20131267; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702896\">10.1038\/sj.bjp.0702896<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702896","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:25:43Z","timestamp":1106943943000},"page":"1259-1267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Voltage\u2010dependent block of normal and mutant muscle sodium channels by 4\u2010Chloro\u2010m\u2010Cresol"],"prefix":"10.1111","volume":"128","author":[{"given":"G","family":"Haeseler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Leuwer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Kavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"W\u00fcrz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Dengler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Piepenbrock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119116"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.107.5.643"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.81.5.613"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02110697"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90271-2"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021684"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199705000-00004"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(73)90341-3"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-199510000-00014"},{"key":"e_1_2_7_12_1","first-page":"3","volume-title":"Testing principles in clinical and preclinical trials","author":"MAURER W.","year":"1995"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020260"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(96)79563-2"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8085162"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.275.2.C389"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199606000-00014"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.49.4.1018"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.26.12785"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0702896","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0702896","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0702896","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T00:01:09Z","timestamp":1698537669000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0702896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,11]]},"references-count":18,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1999,11]]}},"alternative-id":["10.1038\/sj.bjp.0702896"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0702896","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,11]]},"assertion":[{"value":"2009-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}