{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:01:41Z","timestamp":1791291701168,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,1,27]],"date-time":"2005-01-27T00:00:00Z","timestamp":1106784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica Scandinavica"],"published-print":{"date-parts":[[2005,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Aims:\u2002<\/jats:bold> Endothelin\u20101 (ET\u20101) promotes endothelial cell growth. Endothelial cell proliferation involves the activation of Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> channels. In this study, we investigated whether Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> channels with big conductance (BK<jats:sub>Ca<\/jats:sub>) contribute to endothelial cell proliferation induced by ET\u20101.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> The patch\u2010clamp technique was used to analyse BK<jats:sub>Ca<\/jats:sub> activity in endothelial cells derived from human umbilical cord veins (HUVEC). Endothelial proliferation was examined using cell counts and measuring [<jats:sup>3<\/jats:sup>H]\u2010thymidine incorporation. Changes of intracellular Ca<jats:sup>2+<\/jats:sup> levels were examined using fura\u20102 fluorescence imaging.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Characteristic BK<jats:sub>Ca<\/jats:sub> were identified in cultured HUVEC. Continuous perfusion of HUVEC with 10\u2003nmol\u2003L<jats:sup>\u22121<\/jats:sup> ET\u20101 caused a significant increase of BK<jats:sub>Ca<\/jats:sub> open\u2010state probability (<jats:italic>n<\/jats:italic>\u2003=\u200314; <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05; cell\u2010attached patches). The ET<jats:sub>B<\/jats:sub>\u2010receptor antagonist (BQ\u2010788, 1\u2003<jats:italic>\u03bc<\/jats:italic>mol\u2003L<jats:sup>\u22121<\/jats:sup>) blocked this effect. Stimulation with Et\u20101 (10\u2003nmol\u2003L<jats:sup>\u22121<\/jats:sup>) significantly increased cell growth by 69% (<jats:italic>n<\/jats:italic>\u2003=\u200312; <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05). In contrast, the combination of ET\u20101 (10\u2003nmol\u2003L<jats:sup>\u22121<\/jats:sup>) and the highly specific BK<jats:sub>Ca<\/jats:sub> blocker iberiotoxin (IBX; 100\u2003nmol\u2003L<jats:sup>\u22121<\/jats:sup>) did not cause a significant increase in endothelial cell growth. Ca<jats:sup>2+<\/jats:sup> dependency of ET\u20101\u2010induced proliferation was tested using the intracellular Ca<jats:sup>2+<\/jats:sup>\u2010chelator BAPTA (10\u2003<jats:italic>\u03bc<\/jats:italic>mol\u2003L<jats:sup>\u22121<\/jats:sup>). BAPTA abolished ET\u20101 induced proliferation (<jats:italic>n<\/jats:italic>\u2003=\u200312; <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.01). In addition, ET\u20101\u2010induced HUVEC growth was significantly reduced, if cells were kept in a Ca<jats:sup>2+<\/jats:sup>\u2010reduced solution (0.3\u2003mmol\u2003L<jats:sup>\u22121<\/jats:sup>), or by the application of 2 aminoethoxdiphenyl borate (100\u2003<jats:italic>\u03bc<\/jats:italic>mol\u2003L<jats:sup>\u22121<\/jats:sup>) which blocks hyperpolarization\u2010induced Ca<jats:sup>2+<\/jats:sup> entry (<jats:italic>n<\/jats:italic>\u2003=\u200312; <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05).<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> Activation of BK<jats:sub>Ca<\/jats:sub> by ET\u20101 requires ET<jats:sub>B<\/jats:sub>\u2010receptor activation and induces a capacitative Ca<jats:sup>2+<\/jats:sup> influx which plays an important role in ET\u20101\u2010mediated endothelial cell proliferation.<\/jats:p>","DOI":"10.1111\/j.1365-201x.2004.01378.x","type":"journal-article","created":{"date-parts":[[2005,1,27]],"date-time":"2005-01-27T17:13:20Z","timestamp":1106846000000},"page":"161-169","source":"Crossref","is-referenced-by-count":27,"title":["Endothelin\u20101\u2010induced proliferation of human endothelial cells depends on activation of K<sup>+<\/sup> channels and Ca<sup>2+<\/sup> influx"],"prefix":"10.1111","volume":"183","author":[{"given":"C. R. W.","family":"Kuhlmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. K.","family":"Most","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. M.","family":"M\u00fcnz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. A.","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Walther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Raedle\u2010Hurst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Waldecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. M.","family":"Piper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Tillmanns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wiecha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,1,27]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/348730a0"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307258200"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704465"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.61.5.632"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(88)57093-3"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)38560-6"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.6.2367"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.11.4892"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107470"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004330050097"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.51.030189.002125"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10094"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/mvre.1998.2131"},{"key":"e_1_2_15_16_1","first-page":"H686","article-title":"Proliferation and migration of endothelial cells is promoted by endothelins via activation of ETB receptors","volume":"269","author":"Morbidelli L.","year":"1995","journal-title":"Am J Physiol"},{"key":"e_1_2_15_17_1","first-page":"105","article-title":"A role for K+ channels in cell proliferation","volume":"9","author":"Nilius B.","year":"1994","journal-title":"NIPS"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.4.1415"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp018938"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1998.275.4.L729"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.277.4.C746"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0898-6568(90)90069-M"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019318"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/348732a0"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64807-9"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115210"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.81.2.211"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-6374(98)80108-1"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/332411a0"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1159\/000139212"}],"container-title":["Acta Physiologica Scandinavica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-201X.2004.01378.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-201X.2004.01378.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T23:35:52Z","timestamp":1697240152000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-201X.2004.01378.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,1,27]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2005,2]]}},"alternative-id":["10.1111\/j.1365-201X.2004.01378.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-201x.2004.01378.x","archive":["Portico"],"relation":{},"ISSN":["0001-6772","1365-201X"],"issn-type":[{"value":"0001-6772","type":"print"},{"value":"1365-201X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,1,27]]}}}