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| Subject Categories: Membranes & Transport | Cellular Metabolism |
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| The EMBO Journal
(2008) 27, 179–187, doi:10.1038/sj.emboj.7601934 Published online 22 November 2007 |
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| Invalidation of TASK1 potassium channels disrupts adrenal gland zonation and mineralocorticoid homeostasis |
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| Dirk Heitzmann1, 2, Renaud Derand3, Stefan Jungbauer1, Sascha Bandulik1, Christina Sterner1, Frank Schweda1, Abeer El Wakil3, Enzo Lalli3, Nicolas Guy3, Raymond Mengual4, Markus Reichold1, Ines Tegtmeier1, Saïd Bendahhou3, Celso E Gomez-Sanchez5, M Isabel Aller6, William Wisden7, Achim Weber8, Florian Lesage3, Richard Warth1, 9 and Jacques Barhanin3, 9 |
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1 Institute of Physiology, University of Regensburg, Regensburg, Germany 2 Clinic and Policlinic for Internal Medicine II, University of Regensburg, Regensburg, Germany 3 Institut de Pharmacologie Moléculaire et Cellulaire, CNRS and Université de Nice Sophia Antipolis, Valbonne Sophia Antipolis, France 4 Centre Hospitalo-Universitaire de Nice, Nice, France 5 Division of Endocrinology, GV Montgomery VA Medical Center, Jackson, MS, USA 6 Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Cientificas-Universidad Miguel Hernández, San Juan de Alicante, Spain 7 Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK 8 Department of Pathology, University Hospital Zurich, Zurich, Switzerland 9 These authors contributed equally to this work To whom correspondence should be addressed Richard Warth, Institute of Physiology, University of Regensburg, Universitaetsstrasse 31, NWF III—VKL, Regensburg 93053, Germany. Tel.: +49 941 943 2894; Fax: +49 941 943 2896; E-mail: richard.warth@vkl.uni-regensburg.de Received 25 May 2007; Accepted 2 November 2007; Published online 22 November 2007. |
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| Abstract |
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| TASK1 (KCNK3) and TASK3 (KCNK9) are two-pore domain potassium channels highly expressed in adrenal glands. TASK1/TASK3 heterodimers are believed to contribute to the background conductance whose inhibition by angiotensin II stimulates aldosterone secretion. We used task1-/- mice to analyze the role of this channel in adrenal gland function. Task1-/- exhibited severe hyperaldosteronism independent of salt intake, hypokalemia, and arterial 'low-renin' hypertension. The hyperaldosteronism was fully remediable by glucocorticoids. The aldosterone phenotype was caused by an adrenocortical zonation defect. Aldosterone synthase was absent in the outer cortex normally corresponding to the zona glomerulosa, but abundant in the reticulo-fasciculata zone. The impaired mineralocorticoid homeostasis and zonation were independent of the sex in young mice, but were restricted to females in adults. Patch-clamp experiments on adrenal cells suggest that task3 and other K+ channels compensate for the task1 absence. Adrenal zonation appears as a dynamic process that even can take place in adulthood. The striking changes in the adrenocortical architecture in task1-/- mice are the first demonstration of the causative role of a potassium channel in development/differentiation. |
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| Keywords: aldosterone, arterial hypertension, KCNK3, KCNK9, TASK-1 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHThe EMBO Journal Article Aldosterone regulation for 18 years in a case of primary aldosteronism American Journal of Hypertension Correspondence |
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