{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:17:36Z","timestamp":1792667856376,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2950,"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":[[2001,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The effects of <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> block by chromanol 293B and L\u2010735,821 on rabbit QT\u2010interval, action potential duration (APD), and membrane current were compared to those of E\u20104031, a recognized <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub> blocker. Measurements were made in rabbit Langendorff\u2010perfused whole hearts, isolated papillary muscle, and single isolated ventricular myocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Neither chromanol 293B (10\u2003\u03bc<jats:sc>M<\/jats:sc>) nor L\u2010735,821 (100\u2003n<jats:sc>M<\/jats:sc>) had a significant effect on QTc interval in Langendorff\u2010perfused hearts. E\u20104031 (100\u2003n<jats:sc>M<\/jats:sc>), on the other hand, significantly increased QTc interval (35.6\u00b13.9%, <jats:italic>n<\/jats:italic>=8, <jats:italic>P<\/jats:italic>&lt;0.05).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Similarly both chromanol 293B (10\u2003\u03bc<jats:sc>M<\/jats:sc>) and L\u2010735,821 (100\u2003n<jats:sc>M<\/jats:sc>) produced little increase in papillary muscle APD (less than 7%) while pacing at cycle lengths between 300 and 5000\u2003ms. In contrast, E\u20104031 (100\u2003n<jats:sc>M<\/jats:sc>) markedly increased (30\u2003\u2013\u200360%) APD in a reverse frequency\u2010dependent manner.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In ventricular myocytes, the same concentrations of chromanol 293B (10\u2003\u03bc<jats:sc>M<\/jats:sc>), L\u2010735,821 (100\u2003n<jats:sc>M<\/jats:sc>) and E\u20104031 (1\u2003\u03bc<jats:sc>M<\/jats:sc>) markedly or totally blocked <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> and <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub>, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> tail currents activated slowly (at +30\u2003mV, \u03c4=888.1\u00b148.2\u2003ms, <jats:italic>n<\/jats:italic>=21) and deactivated rapidly (at \u221240\u2003mV, \u03c4=157.1\u00b14.7\u2003ms, <jats:italic>n<\/jats:italic>=22), while <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub> tail currents activated rapidly (at +30\u2003mV, \u03c4=35.5\u00b13.1\u2003ms, <jats:italic>n<\/jats:italic>=26) and deactivated slowly (at \u221240\u2003mV, \u03c4<jats:sub>1<\/jats:sub>=641.5\u00b129.0\u2003ms, \u03c4<jats:sub>2<\/jats:sub>=6531\u00b1343, <jats:italic>n<\/jats:italic>=35). <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub> was estimated to contribute substantially more to total current density during normal ventricular muscle action potentials (i.e., after a 150\u2003ms square pulse to +30\u2003mV) than does <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These findings indicate that block of <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> is not likely to provide antiarrhythmic benefit by lengthening normal ventricular muscle QTc, APD, and refractoriness over a wide range of frequencies.<\/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>, 101\u2013110; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703777\">10.1038\/sj.bjp.0703777<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703777","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:06:00Z","timestamp":1106946360000},"page":"101-110","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Pharmacological block of the slow component of the outward delayed rectifier current (<i>I<\/i><sub>Ks<\/sub>) fails to lengthen rabbit ventricular muscle QT<sub>c<\/sub> and action potential duration"],"prefix":"10.1111","volume":"132","author":[{"given":"Csaba","family":"Lengyel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Iost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Vir\u00e1g","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s","family":"Varr\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Lathrop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius Gy","family":"Papp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.1999.tb00667.x"},{"key":"e_1_2_7_3_1","first-page":"212","article-title":"Catecholamines modulate the delayed rectifying potassium current (IK) in guinea pig ventricular myocytes","volume":"410","author":"BENNET P.B.","year":"1987","journal-title":"Pflugers Archiv-Eur. J. Physiol."},{"key":"e_1_2_7_4_1","first-page":"17","article-title":"Selective IKs blockade protects against ventricular fibrillation induced by myocardial ischaemia","volume":"19","author":"BILLMAN G.E.","year":"1998","journal-title":"Eur Heart J."},{"key":"e_1_2_7_5_1","first-page":"1","article-title":"Selective IKs but not IKr blockade protects against ventricular fibrillation induced by myocardial ischaemia","volume":"98","author":"BILLMAN G.E.","year":"1998","journal-title":"Circulation"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00021-2"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050240"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/27.12.2186"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/14.suppl_H.3"},{"key":"e_1_2_7_10_1","first-page":"809","article-title":"Voltage\u2010 and time\u2010dependent block of the delayed K+ current in cardiac myocytes by dofetilide","volume":"262","author":"CARMELIET E.","year":"1992","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00061-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.811bp.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.82.1.289"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.1.26"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2543073"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.t01-2-00391.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1996.sp003961"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1996.sp003962"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199407073310108"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.81.2.686"},{"key":"e_1_2_7_21_1","first-page":"344","article-title":"The rapid and slow component of the delayed rectifier potassium current in undiseased human ventricular myocytes","volume":"20","author":"IOST N.","year":"1999","journal-title":"Eur. Heart J."},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00204-1"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.72.1.75"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1673802"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1139\/y85-248"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.4.689"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.76.3.351"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.18.1917"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1969.sp008689"},{"key":"e_1_2_7_30_1","first-page":"424","article-title":"Low penetrance in the long QT syndrome: the importance of molecular diagnosis","volume":"19","author":"PRIORI S.G.","year":"1998","journal-title":"Eur. Heart J."},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1996.271.6.H2477"},{"key":"e_1_2_7_32_1","first-page":"1","article-title":"The novel Class III antiarrhythmic agent, L\u2010735,821 is a potent and selective blocker of IKs in guinea pig ventricular myocytes","volume":"94","author":"SALATA J.J.","year":"1996","journal-title":"Circulation"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.96.1.195"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.1997.tb01039.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm970517u"},{"key":"e_1_2_7_36_1","first-page":"53","volume-title":"Control of Cardiac Arrhythmias by Lengthening Repolarization","author":"SINGH B.N.","year":"1988"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1970.tb09893.x"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.26.6.661"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(98)00248-4"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.75.5.879"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00067.x"},{"key":"e_1_2_7_42_1","first-page":"183P","article-title":"Does IKs play an important role in repolarization in normal canine and human ventricular muscle and Purkinje fibres","volume":"515","author":"VARR\u00d3 A.","year":"1999","journal-title":"J. Physiol."},{"key":"e_1_2_7_43_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/BF00798257","article-title":"Ionic currents and action potentials in rabbit, rat, and guinea pig ventricular myocytes","volume":"88","author":"VARR\u00d3 A.","year":"1993","journal-title":"Basic Res. Cardiol."},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-198601000-00026"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.2.206"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.93.5.841"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.10.1540"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)00446-W"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0703777","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0703777","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0703777","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T22:57:23Z","timestamp":1697497043000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0703777"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,1]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2001,1]]}},"alternative-id":["10.1038\/sj.bjp.0703777"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0703777","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,1]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}