{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T14:40:46Z","timestamp":1792248046632,"version":"4.4.0"},"reference-count":86,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF18OC0052021"],"award-info":[{"award-number":["NNF18OC0052021"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R344\u20102020\u2010952"],"award-info":[{"award-number":["R344\u20102020\u2010952"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R323\u20102018\u20103674"],"award-info":[{"award-number":["R323\u20102018\u20103674"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Large\u2010conductance, calcium\u2010activated potassium channels (BK channels) and the Na\/K\u2010ATPase are expressed universally in vascular smooth muscle. The Na\/K\u2010ATPase may act via changes in the intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentration mediated by the Na\/Ca exchanger (NCX) and via Src kinase. Both pathways are known to regulate BK channels. Whether BK channels functionally interact in vascular smooth muscle cells with the Na\/K\u2010ATPase remains to be elucidated. Thus, this study addressed the hypothesis that BK channels limit ouabain\u2010induced vasocontraction. Rat mesenteric arteries were studied using isometric myography, FURA\u20102 fluorimetry and proximity ligation assay. The BK channel blocker iberiotoxin potentiated methoxamine\u2010induced contractions. The cardiotonic steroid, ouabain (10\n                    <jats:sup>\u22125<\/jats:sup>\n                    \u2009M), induced a contractile effect of IBTX at basal tension prior to methoxamine administration and enhanced the pro\u2010contractile effect of IBTX on methoxamine\u2010induced contractions. These facilitating effects of ouabain were prevented by the inhibition of either NCX or Src kinase. Furthermore, inhibition of NCX or Src kinase reduced the BK channel\u2010mediated negative feedback regulation of arterial contraction. The effects of NCX and Src kinase inhibition were independent of each other. Co\u2010localization of the Na\/K\u2010ATPase and the BK channel was evident. Our data suggest that BK channels limit ouabain\u2010induced vasocontraction by a dual mechanism involving the NCX and Src kinase signaling. The data propose that the NCX and the Src kinase pathways, mediating the ouabain\u2010induced activation of the BK channel, act in an independent manner.\n                  <\/jats:p>","DOI":"10.1096\/fj.202400628rr","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T11:20:00Z","timestamp":1726053600000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Vascular smooth muscle\n                    <scp>BK<\/scp>\n                    channels limit ouabain\u2010induced vasocontraction: Dual role of the Na\/K\u2010\n                    <scp>ATPase<\/scp>\n                    as a hub for Src\u2010kinase and the Na\/Ca\u2010exchanger"],"prefix":"10.1096","volume":"38","author":[{"given":"Tobias","family":"Orth","sequence":"first","affiliation":[{"name":"Research Division Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim Heidelberg University  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Pyanova","sequence":"additional","affiliation":[{"name":"Physiology, Institute of Theoretical Medicine, Faculty of Medicine University of Augsburg  Augsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lux","sequence":"additional","affiliation":[{"name":"Research Division Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim Heidelberg University  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Research Division Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim Heidelberg University  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Reinheimer","sequence":"additional","affiliation":[{"name":"Research Division Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim Heidelberg University  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8425-8724","authenticated-orcid":false,"given":"Daniel L\u00f8gstrup","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Health Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef Ali","family":"Khalid","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Health Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3276-5887","authenticated-orcid":false,"given":"Salom\u00e9","family":"Rognant","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9903-714X","authenticated-orcid":false,"given":"Thomas A.","family":"Jepps","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3303-1095","authenticated-orcid":false,"given":"Vladimir V.","family":"Matchkov","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Health Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1777-1461","authenticated-orcid":false,"given":"Rudolf","family":"Schubert","sequence":"additional","affiliation":[{"name":"Research Division Cardiovascular Physiology, European Center of Angioscience (ECAS), Medical Faculty Mannheim Heidelberg University  Mannheim Germany"},{"name":"Physiology, Institute of Theoretical Medicine, Faculty of Medicine University of Augsburg  Augsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2017.tb00747.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)01775-2"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004292200"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.222348099"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00371"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.71.102201.141218"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32990-x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.275.5.F633"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20220796"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.3.763"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272419"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00527.2009"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2003.tb07234.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2003.tb07233.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002951200"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e05-08-0735"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22060990"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092600"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106178200"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00347.2016"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13059"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092489"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18761712"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.1007340"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2020.102159"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.033506"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.149500"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.41.1.19"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1176748"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.3.6.691"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.51.4.514"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.149898"},{"key":"e_1_2_10_34_1","first-page":"27","article-title":"Desensitisation to [Ca2+]i by prolonged Na,K\u2010ATPase inhibition is related to depletion of intracellular K+","volume":"28","author":"Nilsson H","year":"2001","journal-title":"J Vasc Res"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)38560-6"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.268.4.C799"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2003.11.029"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2015.139"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1422997112"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP271286"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707284"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.05.002"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13176"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.266866"},{"key":"e_1_2_10_45_1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0022-3565(24)29375-7","article-title":"SEA0400, a novel and selective inhibitor of the Na+\u2010Ca2+ exchanger, attenuates reperfusion injury in the in\u00a0vitro and in\u00a0vivo cerebral ischemic models","volume":"298","author":"Matsuda T","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.FMJ04007X2"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00964.2009"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.37.22391"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(99)80086-0"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80357-3"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-017-1949-3"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1997.tb52251.x"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.108.000711"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200404000-00009"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00673.2011"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1118"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.091801"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.274.1.H27"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5236.633"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050665"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.9.1032"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1159\/000051027"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00728.2010"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.222083"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.265.1.C299"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1373909"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.08.039"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)32067-7"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00362.2022"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12273"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1997.tb52310.x"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00399.2012"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2006.04.031"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00492.2004"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3968"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704574"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00179"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.2.695"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.153593"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2013.116"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200103000-00012"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.013821"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctm.2019.01.007"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.770450"},{"key":"e_1_2_10_85_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0022-3565(25)28488-9","article-title":"Methoxamine as a tool to assess the importance of intraneuronal uptake of l\u2010norepinephrine in the cat's nictitating membrane","volume":"172","author":"Trendelenburg U","year":"1970","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01045.2009"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000262659.09293.56"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202400628RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202400628RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202400628RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T13:46:50Z","timestamp":1792244810000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202400628RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":86,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1096\/fj.202400628RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202400628rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9]]},"assertion":[{"value":"2024-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70046"}}