{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T23:57:10Z","timestamp":1772927830118,"version":"3.50.1"},"reference-count":55,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2016,5,15]]},"abstract":"<jats:p>The kidney is the primary organ ensuring K<jats:sup>+<\/jats:sup>homeostasis. K<jats:sup>+<\/jats:sup>is secreted into the urine in the distal tubule by two mechanisms: by the renal outer medullary K<jats:sup>+<\/jats:sup>channel (K<jats:sub>ir<\/jats:sub>1.1) and by the Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>channel (K<jats:sub>Ca<\/jats:sub>1.1). Here, we report a novel knockout mouse of the \u03b2<jats:sub>2<\/jats:sub>-subunit of the K<jats:sub>Ca<\/jats:sub>1.1 channel (KCNMB2), which displays hyperaldosteronism after decreased renal K<jats:sup>+<\/jats:sup>excretion. KCNMB2<jats:sup>\u2212\/\u2212<\/jats:sup>mice displayed hyperaldosteronism, normal plasma K<jats:sup>+<\/jats:sup>concentration, and produced dilute urine with decreased K<jats:sup>+<\/jats:sup>concentration. The normokalemia indicated that hyperaldosteronism did not result from primary aldosteronism. Activation of the renin-angiotensin-aldosterone system was also ruled out as renal renin mRNA expression was reduced in KCNMB2<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Renal K<jats:sup>+<\/jats:sup>excretion rates were similar in the two genotypes; however, KCNMB2<jats:sup>\u2212\/\u2212<\/jats:sup>mice required elevated plasma aldosterone to achieve K<jats:sup>+<\/jats:sup>balance. Blockade of the mineralocorticoid receptor with eplerenone triggered mild hyperkalemia and unmasked reduced renal K<jats:sup>+<\/jats:sup>excretion in KCNMB2<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Knockout mice for the \u03b1-subunit of the K<jats:sub>Ca<\/jats:sub>1.1 channel (KCNMA1<jats:sup>\u2212\/\u2212<\/jats:sup>mice) have hyperaldosteronism, are hypertensive, and lack flow-induced K<jats:sup>+<\/jats:sup>secretion. KCNMB2<jats:sup>\u2212\/\u2212<\/jats:sup>mice share the phenotypic traits of normokalemia and hyperaldosteronism with KCNMA1<jats:sup>\u2212\/\u2212<\/jats:sup>mice but were normotensive and displayed intact flow-induced K<jats:sup>+<\/jats:sup>secretion. Despite elevated plasma aldosterone, KNCMB2<jats:sup>\u2212\/\u2212<\/jats:sup>mice did not display salt-sensitive hypertension and were able to decrease plasma aldosterone on a high-Na<jats:sup>+<\/jats:sup>diet, although plasma aldosterone remained elevated in KCNMB2<jats:sup>\u2212\/\u2212<\/jats:sup>mice. In summary, KCNMB2<jats:sup>\u2212\/\u2212<\/jats:sup>mice have a reduced ability to excrete K<jats:sup>+<\/jats:sup>into the urine but achieve K<jats:sup>+<\/jats:sup>balance through an aldosterone-mediated, \u03b2<jats:sub>2<\/jats:sub>-independent mechanism. The phenotype of KCNMB2 mice was similar but milder than the phenotype of KCNMA1<jats:sup>\u2212\/\u2212<\/jats:sup>mice.<\/jats:p>","DOI":"10.1152\/ajprenal.00010.2016","type":"journal-article","created":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T03:49:12Z","timestamp":1457581752000},"page":"F1035-F1046","source":"Crossref","is-referenced-by-count":15,"title":["Hyperaldosteronism after decreased renal K<sup>+<\/sup>excretion in KCNMB2 knockout mice"],"prefix":"10.1152","volume":"310","author":[{"given":"Casper K.","family":"Larsen","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Physiology, and Health, Aarhus University, Aarhus, Denmark;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iben S.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Physiology, and Health, Aarhus University, Aarhus, Denmark;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mads V.","family":"Sorensen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Physiology, and Health, Aarhus University, Aarhus, Denmark;"},{"name":"Aarhus Institute for Advanced Studies, Aarhus University, Aarhus, Denmark; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauline I.","family":"de Bruijn","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Physiology, and Health, Aarhus University, Aarhus, Denmark;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Bleich","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Christian-Albrechts-University, Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helle A.","family":"Praetorius","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Physiology, and Health, Aarhus University, Aarhus, Denmark;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Leipziger","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Physiology, and Health, Aarhus University, Aarhus, Denmark;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(92)90101-B"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141233398"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000388"},{"key":"B4","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S0026-895X(25)12929-5","volume":"40","author":"Balla T","year":"1991","journal-title":"Mol Pharmacol"},{"key":"B5","first-page":"17","volume":"4","author":"Benchetrit S","year":"2002","journal-title":"Isr Med Assoc J"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1460523"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(84)90302-4"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.27.5.1121"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00490.2012"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.154435"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00002.2008"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03419"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90528.2008"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00585.2014"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90527.2008"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.274.5.F817"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1994.tb02519.x"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00018.2007"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904635106"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1295438"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601934"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009080817"},{"key":"B23","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1152\/ajplegacy.1967.212.6.1365","volume":"212","author":"Kahn M","year":"1967","journal-title":"Am J Physiol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3791\/51582"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-002-1070-0"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00057.2007"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90685.2008"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00217.2002"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0151"},{"key":"B30","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1681\/ASN.V8121823","volume":"8","author":"Mennitt PA","year":"1997","journal-title":"J Am Soc Nephrol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00057.2005"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200409236"},{"key":"B33","first-page":"156","volume":"17","author":"Orio P","year":"2002","journal-title":"News Physiol Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1991.261.4.F696"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.104.4.693"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00191.2006"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00340.2004"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002369"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.07.059"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.272880"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002438"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000156448.74296.FE"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00439.2005"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.14"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.181933"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-012-1104-0"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00592.2010"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2013.04.002"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00171.2013"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.5.F786"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00191.2003"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/nature09162"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205435109"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.010908.163241"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00010.2016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T18:27:22Z","timestamp":1748802442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00010.2016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,15]]},"references-count":55,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,5,15]]}},"alternative-id":["10.1152\/ajprenal.00010.2016"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00010.2016","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,15]]}}}