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. 2019 Dec 28;21(1):221. doi: 10.3390/ijms21010221

Figure 2.

Figure 2

(a) Aldosterone-mediated induction of channel-activating protease 1 (Cap1) activates Na+ reabsorption, but simultaneously inhibits the paracellular “chloride shunt”, resulting in excessive K+ excretion. When aldosterone is secreted (1), it triggers the expression of Cap1 in principal cells of the renal collecting duct (2). Cap1 inhibits Cl− reabsorption directly by disrupting trans-interactions of Cldn-4. Simultaneously, Cap1 activates apical Na+ channels (ENaC), and thus, increases the transcellular reabsorption of Na+ (3). Consequently, the growing luminal negative potential drives K+ secretion into the urine via renal outer medullary potassium (ROMK) channels (4). (b) Aldosterone activates ENaC, ROMK, and the paracellular “chloride shunt” via with no lysine kinases 4 (WNK4) phosphorylation. When aldosterone is secreted (1), it leads to the phosphorylation of WNK4. This suspends the tonic inhibition of ROMK and ENaC by WNK4 (2). Furthermore, WNK4 phosphorylates claudins located to the tight junctions (TJs) of the renal collecting duct and thereby increases Cl− reabsorption (3). Green arrows indicate positive regulation, red lines indicate inhibition.