title: Task3 potassium channel gene invalidation causes low renin and salt-sensitive arterial hypertension.
abstract: Task1 and Task3 potassium channels (Task: tandem of P domains in a weak inward rectifying K(+) channel-related acid-sensitive K(+) channel) are believed to control the membrane voltage of aldosterone-producing adrenal glomerulosa cells. This study aimed at understanding the role of Task3 for the control of aldosterone secretion. The adrenal phenotype of Task3(-/-) mice was investigated using electrophysiology, adrenal slices, and blood pressure measurements. Primary adrenocortical cells of Task3(-/-) mice were strongly depolarized compared with wild-type (-52 vs. -79 mV), and in fresh adrenal slices Ca(2+) signaling of Task3(-/-) glomerulosa cells was abnormal. In living Task3(-/-) mice, the regulation of aldosterone secretion showed specific deficits: Under low Na(+) and high K(+) diets, protocols known to increase aldosterone, and under standard diet, Task3 inactivation was compensated and aldosterone was normal. However, high Na(+) and low K(+) diets, two protocols known to lower aldosterone, failed to lower aldosterone in Task3(-/-) mice. The physiological regulation of aldosterone was disturbed: aldosterone-renin ratio, an indicator of autonomous aldosterone secretion, was 3-fold elevated at standard and high Na(+) diets. Isolated adrenal glands of Task3(-/-) produced 2-fold more aldosterone. As a consequence, Task3(-/-) mice showed salt-sensitive arterial hypertension (plus 10 mm Hg). In conclusion, Task3 plays an important role in the adaptation of aldosterone secretion to dietary salt intake.
authors.affiliation: University of Regensburg, 93053 Regensburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Penton
authors.forename: Sascha
authors.initials: S
authors.lastname: Bandulik
authors.forename: Frank
authors.initials: F
authors.lastname: Schweda
authors.forename: Sophia
authors.initials: S
authors.lastname: Haubs
authors.forename: Philipp
authors.initials: P
authors.lastname: Tauber
authors.forename: Markus
authors.initials: M
authors.lastname: Reichold
authors.forename: Lu Dang
authors.initials: LD
authors.lastname: Cong
authors.forename: Abeer
authors.initials: A
authors.lastname: El Wakil
authors.forename: Thomas
authors.initials: T
authors.lastname: Budde
authors.forename: Florian
authors.initials: F
authors.lastname: Lesage
authors.forename: Enzo
authors.initials: E
authors.lastname: Lalli
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Zennaro
authors.forename: Richard
authors.initials: R
authors.lastname: Warth
authors.forename: Jacques
authors.initials: J
authors.lastname: Barhanin
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D012083:Renin / Q000097:blood*; D017673:Sodium Chloride, Dietary; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D017673:Sodium Chloride, Dietary; C511784:TASK3 protein, mouse; D000450:Aldosterone; D012083:Renin; D002118:Calcium