title: Invalidation of TASK1 potassium channels disrupts adrenal gland zonation and mineralocorticoid homeostasis.
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.
authors.affiliation: Institute of Physiology, University of Regensburg, Regensburg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Heitzmann
authors.forename: Renaud
authors.initials: R
authors.lastname: Derand
authors.forename: Stefan
authors.initials: S
authors.lastname: Jungbauer
authors.forename: Sascha
authors.initials: S
authors.lastname: Bandulik
authors.forename: Christina
authors.initials: C
authors.lastname: Sterner
authors.forename: Frank
authors.initials: F
authors.lastname: Schweda
authors.forename: Abeer
authors.initials: A
authors.lastname: El Wakil
authors.forename: Enzo
authors.initials: E
authors.lastname: Lalli
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guy
authors.forename: Raymond
authors.initials: R
authors.lastname: Mengual
authors.forename: Markus
authors.initials: M
authors.lastname: Reichold
authors.forename: Ines
authors.initials: I
authors.lastname: Tegtmeier
authors.forename: Saïd
authors.initials: S
authors.lastname: Bendahhou
authors.forename: Celso E
authors.initials: CE
authors.lastname: Gomez-Sanchez
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Aller
authors.forename: William
authors.initials: W
authors.lastname: Wisden
authors.forename: Achim
authors.initials: A
authors.lastname: Weber
authors.forename: Florian
authors.initials: F
authors.lastname: Lesage
authors.forename: Richard
authors.initials: R
authors.lastname: Warth
authors.forename: Jacques
authors.initials: J
authors.lastname: Barhanin
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism* / Q000473:pathology; D000450:Aldosterone / Q000097:blood / Q000378:metabolism; D000818:Animals; D005260:Female; D006706:Homeostasis / Q000235:genetics*; D006929:Hyperaldosteronism / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008901:Mineralocorticoids / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics*; D011188:Potassium / Q000097:blood; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics*; D012083:Renin / Q000097:blood
chemical_list: D008901:Mineralocorticoids; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D000450:Aldosterone; D012083:Renin; D011188:Potassium