The importance of adrenal K⁺ channel function for the control of aldosterone secretion, adrenocortical zonation, and adenoma formation was recently highlighted by findings from knockout mice as well as human genetics. In this study, we took advantage of the age-dependent adrenal phenotype displayed by the Task3^-/- mouse to figure out how Task3 K⁺ channels contribute to mineralocorticoid and glucocorticoid homeostasis, and to adrenal development.

Newborn Task3^-/- mice had an aggravated adrenal phenotype compared to adult mice and exhibited strongly increased plasma levels of aldosterone, corticosterone, and progesterone. This general adrenocortical dysfunction of neonate Task3^-/- mice was accompanied by a remarkable abnormal adrenal expression of the protease renin, which is normally mainly expressed in the kidney. The activation of the local adrenal renin-system was paralleled by an increased adrenal expression of genes which are known to stimulate steroid hormone synthesis and, thereby, could participate in the autonomous aldosterone secretion of Task3^-/- mice. Furthermore, we identified factors which might compensate for the Task3 deletion in adult mice. Similar to Task3, these factors could be modulators of aldosterone secretion in humans.