{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:24:18Z","timestamp":1791095058564,"version":"4.1.0"},"reference-count":47,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,4,1]]},"abstract":"<jats:p>Primary aldosteronism is the most common cause of secondary hypertension, most frequently due to an aldosterone-producing adenoma or idiopathic hyperaldosteronism. Somatic mutations of the potassium channel KCNJ5 in the region of the selectivity filter have been found in a significant number of aldosterone-producing adenomas. There are also familial forms of primary aldosteronism, one of which, familial hyperaldosteronism type 3 which to date has been found in one family who presented with a severe abnormality in aldosterone and 18-oxocortisol production and hypertrophy and hyperplasia of the transitional zone of the adrenal cortex. In familial hyperaldosteronism type 3, there is a genomic mutation causing a T158A change of amino acids within the selectivity filter region of the KCNJ5 gene.<\/jats:p>\n               <jats:p>We are reporting our studies demonstrating that lentiviral-mediated expression of a gene carrying the T158A mutation of the KCNJ5 in the HAC15 adrenal cortical carcinoma cell line causes a 5.3-fold increase in aldosterone secretion in unstimulated HAC15-KCNJ5 cells and that forskolin-stimulated aldosterone secretion was greater than that of angiotensin II. Expression of the mutated KCNJ5 gene decreases plasma membrane polarization, allowing sodium and calcium influx into the cells. The calcium channel antagonist nifedipine and the calmodulin inhibitor W-7 variably inhibited the effect. Overexpression of the mutated KCNJ5 channel resulted in a modest decrease in HAC15 cell proliferation.<\/jats:p>\n               <jats:p>These studies demonstrate that the T158A mutation of the KCNJ5 gene produces a marked stimulation in aldosterone biosynthesis that is dependent on membrane depolarization and sodium and calcium influx into the HAC15 adrenal cortical carcinoma cells.<\/jats:p>","DOI":"10.1210\/en.2011-1733","type":"journal-article","created":{"date-parts":[[2012,2,8]],"date-time":"2012-02-08T07:19:17Z","timestamp":1328685557000},"page":"1774-1782","source":"Crossref","is-referenced-by-count":162,"title":["Potassium Channel Mutant KCNJ5 T158A Expression in HAC-15 Cells Increases Aldosterone Synthesis"],"prefix":"10.1210","volume":"153","author":[{"given":"Kenji","family":"Oki","sequence":"first","affiliation":[{"name":"Research and Medical Service (K.O., M.W.P., M.L.L., E.P.G.-S., C.E.G.-S.), Jackson, Mississippi 39216"},{"name":"G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Division of Endocrinology (K.O., M.W.P., M.L.L., E.P.G.-S., C.E.G.-S.), Jackson, Mississippi 39216"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria W.","family":"Plonczynski","sequence":"first","affiliation":[{"name":"Research and Medical Service (K.O., M.W.P., M.L.L., E.P.G.-S., C.E.G.-S.), Jackson, Mississippi 39216"},{"name":"G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Division of Endocrinology (K.O., M.W.P., M.L.L., E.P.G.-S., C.E.G.-S.), Jackson, Mississippi 39216"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milay","family":"Luis Lam","sequence":"first","affiliation":[{"name":"Research and Medical Service (K.O., M.W.P., M.L.L., E.P.G.-S., C.E.G.-S.), Jackson, Mississippi 39216"},{"name":"G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Division of Endocrinology (K.O., M.W.P., M.L.L., E.P.G.-S., C.E.G.-S.), Jackson, Mississippi 39216"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise P.","family":"Gomez-Sanchez","sequence":"first","affiliation":[{"name":"Research and Medical Service (K.O., M.W.P., M.L.L., E.P.G.-S., C.E.G.-S.), Jackson, Mississippi 39216"},{"name":"G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Division of Endocrinology (K.O., M.W.P., M.L.L., E.P.G.-S., C.E.G.-S.), Jackson, Mississippi 39216"},{"name":"Department of Medicine, Department of Pharmacology (E.P.G.-S.), The University of Mississippi Medical Center, Jackson, Mississippi 39216"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso E.","family":"Gomez-Sanchez","sequence":"first","affiliation":[{"name":"Research and Medical Service (K.O., M.W.P., M.L.L., E.P.G.-S., C.E.G.-S.), Jackson, Mississippi 39216"},{"name":"G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Division of Endocrinology (K.O., M.W.P., M.L.L., E.P.G.-S., C.E.G.-S.), Jackson, Mississippi 39216"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2012,2,7]]},"reference":[{"key":"2020071612111304000_B1","doi-asserted-by":"crossref","first-page":"3266","DOI":"10.1210\/jc.2008-0104","article-title":"Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline.","volume":"93","author":"Funder","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612111304000_B2","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.jacc.2005.01.015","article-title":"Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism.","volume":"45","author":"Milliez","year":"2005","journal-title":"J Am Coll 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