Heitzmann, Dirk and Derand, Renaud and Jungbauer, Stefan and Bandulik, Sascha and Sterner, Christina and Schweda, Frank and El Wakil, Abeer and Lalli, Enzo and Guy, Nicolas and Mengual, Raymond and Reichold, Markus and Tegtmeier, Ines and Bendahhou, Said and Gomez-Sanchez, Celso E. and Aller, M. Isabel and Wisden, William and Weber, Achim and Lesage, Florian and Warth, Richard and Barhanin, Jacques (2008) Invalidation of TASK1 potassium channels disrupts adrenal gland zonation and mineralocorticoid homeostasis. EMBO JOURNAL, 27 (1). pp. 179-187. ISSN 0261-4189, 1460-2075
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLUCOCORTICOID-REMEDIABLE ALDOSTERONISM; CHIMERIC GENE DUPLICATIONS; GLOMERULOSA CELLS; ANGIOTENSIN-II; MEMBRANE DEPOLARIZATION; FUNCTIONAL ZONATION; DEFICIENT MICE; K+ CHANNEL; EXPRESSION; SECRETION; aldosterone; arterial hypertension; KCNK3; KCNK9; TASK-1 |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Nov 2020 10:46 |
| Last Modified: | 10 Nov 2020 10:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/31511 |
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