Endocrine Abstracts

Potassium channels control the membrane voltage of aldosterone-producing zona glomerulosa cells in the adrenal glands. They are necessary for the unique K+ sensitivity of these cells and targets of angiotensin II signaling. The 2-P-domain K+ channels TASK1 and TASK3 are among those K+ channels that exhibit strongest expression levels in the adrenal gland. Knockout mice for TASK1 and TASK3 have highlighted the functional relevance of these channels: In young mice before puberty, invalidation of the TASK1 gene resulted in autonomous aldosterone production and caused an aberrant expression of aldosterone synthase in zona fasciculata cells that normally produce only glucocorticoids. After puberty, male mice were able to compensate for the defect of TASK1 and their aldosterone synthase regained regular localization in glomerulosa cells. In female TASK1 knockout mice, dyszonation of the aldosterone synthase and hyperaldosteronism persisted after puberty. TASK3 knockout mice presented regular localization of the aldosterone synthase and normal plasma aldosterone levels under control conditions. However, plasma renin activity was suppressed and the aldosterone/renin ratio, an indicator of autonomous aldosterone production, was elevated. Under high Na+ diet, TASK3 knockout animals were unable to reduce aldosterone production appropriately. The impaired regulation of aldosterone levels under high dietary salt resulted in salt-induced arterial hypertension. These data corroborated the concept that TASK K+ channels play an important role in adrenocortical cells. Dysfunction of TASK channels can lead to developmental deficits such as aberrant expression of aldosterone synthase, to hyperaldosteronism, and to maladaptation of aldosterone secretion to dietary salt intake.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: Declaration of Funding: Deutsche Forschungsgemeinschaft (FOR1086).