Aldosterone plays a central role in various pathological conditions including hypertension. Primary aldosteronism (autonomous aldosterone production from the adrenal cortex) causes the most common form of secondary arterial hypertension. Recent studies have highlighted the TWIK (Tandem of pore domains in a Weak Inward rectifying potassium channel)-related acid-sensitive potassium channel 1 (Task1) knockout mice a valuable tool to study the control of aldosterone production. These mice are characterized by primary aldosteronism associated with ectopic expression of Cyp11b2 in the zona fasciculata of only adult female Task1-/- adrenals. Herein, it was hypothesized that the depolarized state of Task1-/- mice is sufficient to activate the low threshold Ca2+ channels, the so-called Cav3.2 channels, leading to excessive entry of Ca2+. This rise in Ca2+ is probably responsible for the lack of functional zonation in these mice. To evaluate this hypothesis, we investigated the impact of inactivation of Cav3.2 in a background deficient for Task1-/- upon both aldosterone production as well as adrenocortical zonation. The results of the present study revealed that the phenotype of the female Task1-/- mice persisted even in the absence of Cav3.2. However, a remarkable decrease of aldosterone synthase-positive cells was observed in female compound Task1/Cav3.2 null mice which unlike Task1-/- mice were able to retrieve their physiological control upon aldosterone secretion under potassium-rich diet. These data suggest that compensatory mechanisms regulating the excessive ectopic expression of aldosterone are partially present in adult female Task1/Cav3.2-/- mice without restoring normal zonation pattern but they are totally absent in adult female Task1-/- mice. Further studies are required to define the detailed pathways that activate and repress aldosterone production under normal and pathological conditions.
Task1, adrenal gland, Cav3.2, aldosterone production, adrenal zonation