{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T08:26:34Z","timestamp":1758875194255},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3134,"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":[[2000,7]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>We studied the effects of benzylalcohol on heterologously expressed wild type (WT), paramyotonia congenita (R1448H) and hyperkalaemic periodic paralysis (M1360V) mutant \u03b1\u2010subunits of human skeletal muscle sodium channels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Benzylalcohol blocked rested channels at \u2212150\u2003mV membrane potential, with an ECR<jats:sub>50<\/jats:sub> of 5.3\u2003m<jats:sc>M<\/jats:sc> in wild type, 5.1\u2003m<jats:sc>M<\/jats:sc> in R1448H, and 6.2\u2003m<jats:sc>M<\/jats:sc> in M1360V. When blockade was assessed at \u2212100\u2003mV, the ECR<jats:sub>50<\/jats:sub> was reduced in R1448H (2\u2003m<jats:sc>M<\/jats:sc>) compared with both wild type (4.3\u2003m<jats:sc>M<\/jats:sc>; <jats:italic>P<\/jats:italic>&lt;0.01) and M1360V (4.3\u2003m<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Membrane depolarization before the test depolarization significantly promoted benzylalcohol\u2010induced sodium channel blockade. The values of <jats:italic>K<jats:sub>D<\/jats:sub><\/jats:italic> for the fast\u2010inactivated state derived from benzylalcohol\u2010induced shifts in steady\u2010state availability curves were 0.66\u2003m<jats:sc>M<\/jats:sc> in wild type and 0.58\u2003m<jats:sc>M<\/jats:sc> in R1448H. In the presence of slow inactivation induced by 2.5\u2003s depolarizing prepulses, the ECI<jats:sub>50<\/jats:sub> for benzylalcohol\u2010induced current inhibition was 0.59\u2003m<jats:sc>M<\/jats:sc> in wild type and 0.53\u2003m<jats:sc>M<\/jats:sc> in R1448H.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Recovery from fast inactivation was prolonged in the presence of drug in all clones.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Benzylalcohol induced significant frequency\u2010dependent block at stimulating frequencies of 10, 50, and 100\u2003Hz in all clones.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our results clearly show that benzylalcohol is an effective blocker of muscle sodium channels in conditions that are associated with membrane depolarization. Mutants that enter voltage\u2010dependent inactivation at more hyperpolarized membrane potentials compared with wild type are more sensitive to inhibitory effects at the normal resting potential.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>130<\/jats:bold>, 1321\u20131330; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703447\">10.1038\/sj.bjp.0703447<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703447","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:16:10Z","timestamp":1106946970000},"page":"1321-1330","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Voltage\u2010dependent blockade of normal and mutant muscle sodium channels by benzylalcohol"],"prefix":"10.1111","volume":"130","author":[{"given":"G","family":"Haeseler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Mamarvar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Bufler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Dengler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Hecker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J K","family":"Aronson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Piepenbrock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Leuwer","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":"10.1085\/jgp.107.5.643"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.81.5.613"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1542\/peds.77.4.507","article-title":"Benzyl alcohol toxicity: impact on neurologic handicaps among surviving very low birth weight infants","volume":"77","author":"BENDA G.I.","year":"1986","journal-title":"Pediactrics"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00585952"},{"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":"10.1016\/0042-6822(73)90341-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702896"},{"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":"10.1006\/taap.1995.1154"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(71)90315-2"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-199510000-00014"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/106002809502900616"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600750718"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0742-8413(91)90269-Y"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020260"},{"key":"e_1_2_7_18_1","first-page":"566","article-title":"Acute intravenous toxicity of dimethyl sulfoxide, polythylene glycol 400, dimethylformamide, absolute ethanol, and benzyl alcohol in inbred mouse strains","volume":"44","author":"MONTAGUTI P.","year":"1994","journal-title":"Arzneim. 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