Aldosterone, SGK1, and ion channels in the kidney

Abstract

Hyperaldosteronism, a common cause of hypertension, is strongly connected to Na ⁺, K ⁺, and Mg ²⁺ dysregulation. Owing to its steroidal structure, aldosterone is an active transcriptional modifier when bound to the mineralocorticoid receptor (MR) in cells expressing the enzyme 11β-hydroxysteroid dehydrogenase 2, such as those comprising the aldosterone-sensitive distal nephron (ASDN). One such up-regulated protein, the ubiquitous serum and glucocorticoid regulated kinase 1 (SGK1), has the capacity to modulate the surface expression and function of many classes of renal ion channels, including those that transport Na ⁺ (ENaC), K ⁺ (ROMK/BK), Ca ²⁺ (TRPV4/5/6), Mg ²⁺ (TRPM7/6), and Cl ⁻ (ClC-K, CFTR). Here, we discuss the mechanisms by which ASDN expressed channels are up-regulated by SGK1, while highlighting newly discovered pathways connecting aldosterone to nonselective cation channels that are permeable to Mg ²⁺ (TRPM7) or Ca ²⁺ (TRPV4).