Task3 potassium channel gene invalidation causes low renin and salt-sensitive arterial hypertension

D Penton, S Bandulik, F Schweda, S Haubs… - …, 2012 - academic.oup.com
D Penton, S Bandulik, F Schweda, S Haubs, P Tauber, M Reichold, LD Cong, A El Wakil
Endocrinology, 2012academic.oup.com
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 …
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 Ca2+ 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.
Oxford University Press