{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:28:57Z","timestamp":1791217737881,"version":"4.1.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,2,12]]},"abstract":"<jats:p>\n                    When inappropriate for salt status, the mineralocorticoid aldosterone induces cardiac and renal injury. Autonomous overproduction of aldosterone from the adrenal zona glomerulosa (ZG) is also the most frequent cause of secondary hypertension. Yet, the etiology of nontumorigenic primary hyperaldosteronism caused by bilateral idiopathic hyperaldosteronism remains unknown. Here, we show that genetic deletion of TWIK-related acid-sensitive K (TASK)-1 and TASK-3 channels removes an important background K current that results in a marked depolarization of ZG cell membrane potential. Although TASK channel deletion mice (TASK\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) adjust urinary Na excretion and aldosterone production to match Na intake, they produce more aldosterone than control mice across the range of Na intake. Overproduction of aldosterone is not the result of enhanced activity of the renin\u2013angiotensin system because circulating renin concentrations remain either unchanged or lower than those of control mice at each level of Na intake. In addition, TASK\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice fail to suppress aldosterone production in response to dietary Na loading. Autonomous aldosterone production is also demonstrated by the failure of an angiotensin type 1 receptor blocker, candesartan, to normalize aldosterone production to control levels in TASK\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Thus, TASK\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    channel knockout mice exhibit the hallmarks of primary hyperaldosteronism. Our studies establish an animal model of nontumorigenic primary hyperaldosteronism and identify TASK channels as a possible therapeutic target for primary hyperaldosteronism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0712000105","type":"journal-article","created":{"date-parts":[[2008,2,4]],"date-time":"2008-02-04T20:59:53Z","timestamp":1202158793000},"page":"2203-2208","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":180,"title":["TASK channel deletion in mice causes primary hyperaldosteronism"],"prefix":"10.1073","volume":"105","author":[{"given":"Lucinda A.","family":"Davies","sequence":"first","affiliation":[{"name":"Departments of *Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlong","family":"Hu","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick A.","family":"Guagliardo","sequence":"additional","affiliation":[{"name":"Internal Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Sen","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Chen","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund M.","family":"Talley","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Carey","sequence":"additional","affiliation":[{"name":"Internal Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Bayliss","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology,"},{"name":"Anesthesiology, University of Virginia School of Medicine, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Q.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology,"},{"name":"Anesthesiology, University of Virginia School of Medicine, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,2,12]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-121-11-199412010-00010"},{"key":"e_1_3_3_2_2","first-page":"1863","article-title":"Primary hyperaldosteronism in essential hypertensives: Prevalence, biochemical profile, and molecular biology.","volume":"85","author":"Fardella CE","year":"2000","unstructured":"CE Fardella, et al., Primary hyperaldosteronism in essential hypertensives: Prevalence, biochemical profile, and molecular biology. 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