{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:41:49Z","timestamp":1791283309583,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2015,5,15]],"date-time":"2015-05-15T00:00:00Z","timestamp":1431648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31271210"],"award-info":[{"award-number":["31271210"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Program for University Innovation Team Leading Talent of Hebei Province","award":["LJRC019"],"award-info":[{"award-number":["LJRC019"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>There is emerging evidence that the mineralocorticoid hormone aldosterone is associated with arrhythmias in cardiovascular disease. However, the effect of aldosterone on the slowly activated delayed rectifier potassium current (<jats:styled-content style=\"fixed-case\">I<jats:sub>K<\/jats:sub><\/jats:styled-content><jats:sub>s<\/jats:sub>) remains poorly understood. The present study was designed to investigate the modulation of <jats:styled-content style=\"fixed-case\">I<jats:sub>K<\/jats:sub><\/jats:styled-content><jats:sub>s<\/jats:sub> by aldosterone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Adult guinea pigs were treated with aldosterone for 28 days via osmotic pumps. Standard glass microelectrode recordings and whole\u2010cell patch\u2010clamp techniques were used to record action potentials in papillary muscles and <jats:styled-content style=\"fixed-case\">I<jats:sub>K<\/jats:sub><\/jats:styled-content><jats:sub>s<\/jats:sub> in ventricular cardiomyocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The aldosterone\u2010treated animals exhibited a prolongation of the <jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content> interval and action potential duration with a higher incidence of early afterdepolarizations. Patch\u2010clamp recordings showed a significant down\u2010regulation of <jats:styled-content style=\"fixed-case\">I<jats:sub>K<\/jats:sub><\/jats:styled-content><jats:sub>s<\/jats:sub> density in the ventricular myocytes of these treated animals. These aldosterone\u2010induced electrophysiological changes were fully prevented by a combined treatment with spironolactone, a mineralocorticoid receptor (<jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content>) antagonist. In addition, in <jats:italic>in vitro<\/jats:italic> cultured ventricular cardiomyocytes, treatment with aldosterone (sustained exposure for 24\u2009h) decreased the <jats:styled-content style=\"fixed-case\">I<jats:sub>K<\/jats:sub><\/jats:styled-content><jats:sub>s<\/jats:sub> density in a concentration\u2010dependent manner. Furthermore, a significant corresponding reduction in the mRNA\/protein expression of IKs channel pore and auxiliary subunits, KCNQ1 and KCNE1 was detected in ventricular tissue from the aldosterone\u2010treated animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Aldosterone down\u2010regulates <jats:styled-content style=\"fixed-case\">I<jats:sub>K<\/jats:sub><\/jats:styled-content><jats:sub>s<\/jats:sub> by inhibiting the expression of <jats:styled-content style=\"fixed-case\">KCNQ<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">KCNE<\/jats:styled-content>1, thus delaying the ventricular repolarization. These results provide new insights into the mechanism underlying <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content><jats:sup>+<\/jats:sup> channel remodelling in heart disease and may explain the highly beneficial effects of <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> antagonists in <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/bph.2015.172.issue-23\">http:\/\/dx.doi.org\/10.1111\/bph.2015.172.issue-23<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13163","type":"journal-article","created":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T10:07:15Z","timestamp":1428487635000},"page":"5596-5608","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Aldosterone down\u2010regulates the slowly activated delayed rectifier potassium current in adult guinea pig cardiomyocytes"],"prefix":"10.1111","volume":"172","author":[{"given":"Yankun","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Pharmacology Hebei Medical University The Key Laboratory of New Drug Pharmacology and Toxicology  Shijiazhuang Hebei China"},{"name":"Heart Center Hebei General Hospital  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Hebei Medical University The Key Laboratory of New Drug Pharmacology and Toxicology  Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Hebei Medical University The Key Laboratory of New Drug Pharmacology and Toxicology  Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Hebei Medical University The Key Laboratory of New Drug Pharmacology and Toxicology  Shijiazhuang Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology 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