Figure 1. Regulation of aldosterone production.

Increase of intracellular calcium concentration is the convergence point of the main physiological stimuli of aldosterone secretion (angiotensin II – AngII-, increased plasma K⁺ concentration, and adrenocorticotropic hormone). Binding of AngII to its receptor (AT1R) increases intracellular calcium concentration by inhibiting the two-P-domain K⁺ channels (TASK), which in turn leads to cell membrane depolarization and opening of voltage-gated calcium channels. Intracellular Ca²⁺ binds to calmodulin and increases the transcription of CYP11B2 (encoding aldosterone synthase, the last rate-limiting enzyme for aldosterone production) through the activation of its main transcriptional factors (NURR-1, ATF, CREB). GIRK4, Na⁺/K⁺ ATPase, Ca²⁺ ATPase3 and Cav1.3 are shown in their physiological role and effects on intracellular ion homeostasis. NURR-1, nuclear receptor related 1; ATF, activating transcription factor; CREB, cAMP response element-binding protein; GIRK4, G-protein-activated inwardly rectifying K+ channel.