1. Renal potassium physiology: integration of the renal response to dietary potassium depletion 
Kamel S. Kamel, Martin Schreiber, Mitchell L. Halperin 
Kidney International 
Volume 93, Issue 1, Pages (January 2018)
DOI: /j.kint
Copyright © 2017 International Society of Nephrology Terms and Conditions

2. Figure 1
Effect of K+ depletion on the ENaC and ROMK. The T-shaped dashed modified arrow structures represent removal of an inhibitory effect. Hypokalemia inhibits aldosterone production. As less aldosterone (denoted by the dotted circle) binds to the mineralocorticoid receptor, transcription of SGK1 is decreased (dashed arrow). Abundance of the ENaC in the luminal membrane of principal cells is diminished, as when the SGK1 level is low, NEDD4-2 ubiquinates the ENaC, which results in its targeting to the proteasome for degradation. A number of mechanisms lead to the decreased abundance of ROMK in the luminal membrane of principal cells by inducing its endocytosis. Both Ang II and K+ depletion lead to endocytosis of ROMK via the production of superoxide anion and increased expression of the Src family of PTK. When the SGK1 level is low, WNK4 exerts its effect to induce ROMK endocytosis. The ratio of mRNA KS-WNK1 to L-WNK1 is decreased by dietary K+ restriction; L-WNK1 exerts its effect to cause endocytosis of ROMK. Aldo, aldosterone; Ang II, angiotensin II; ENaC, epithelial sodium channels; KS-WNK1, kidney-specific WNK1; L-WNK1, long WNK1; MR, mineralocorticoid receptor; P K, concentration of K+ in plasma; PTK, protein tyrosine kinases; ROMK, renal outer medullary potassium channel; SGK1, serum and glucocorticoid regulated kinase 1; WNK, with-no-lysine kinase.
Kidney International  , 41-53DOI: ( /j.kint )
Copyright © 2017 International Society of Nephrology Terms and Conditions

3. Figure 2
Activation of WNK-SPAK/OSR1-NCC during K+ depletion. The T-shaped, dashed modified arrow structures represent removal of an inhibitory effect. Hypokalemia is associated with an increase in Ang II, which converts WNK4 to an NCC-activating kinase. Dietary K+ restriction causes a reduced ratio of KS-WNK1 to L-WNK1 transcripts; hence, L-WNK1 exerts its effect to activate the SPAK/OSR1-NCC. Lowering the extracellular concentration of K+ and the effect of Ang II to activate Kir4.1/Kir5.1 increase the outward flux of K+ across the basolateral membrane. This leads to the hyperpolarization of the basolateral membrane potential, which increases the exit of Cl− via the basolateral Cl− ion channel ClC-K2 and hence a decrease in the intracellular concentration of Cl−. In the presence of a low intracellular concentration of Cl−, WNK4 is autophosphorylated and its blocking effect on WNK1 is removed. Phosphorylated WNK4 and WNK1 (denoted by the letter P) phosphorylate SPAK/OSR1, which in turn phosphorylate and activate the NCC. Ang II, angiotensin II; ClC-K2, chloride channel-K2; DCT, distal convoluted tubule; KS-WNK1, kidney-specific WNK1; L-WNK1, long WNK1; NCC, sodium chloride cotransporter; P K, concentration of K+ in plasma; SPAK, STE20-related proline-alanine–rich kinase; OSR1, oxidative stress response kinase type 1; WNK, with-no-lysine kinase.
Kidney International  , 41-53DOI: ( /j.kint )
Copyright © 2017 International Society of Nephrology Terms and Conditions

4. Figure 3
Reabsorption of K+ in the medullary collecting duct (MCD). The reabsorption of K+ is stimulated by K+ depletion and is mediated by H+/K+-ATPase type 2. This requires the presence of H+ acceptors in the luminal fluid. Hypokalemia is associated with intracellular acidosis in cells of the proximal convoluted tubule, which stimulates production of NH4+ and also increases the expression of Rh C glycoprotein (Rhcg) in the MCD. As a result, NH3 is the H+ ion acceptor in the lumen of the MCD in this setting. The exit of K+ and Cl− from the cell could be via a K+/Cl− cotransporter or separate K+ and Cl− channels (not shown). Cl− re-enters the cell in exchange for HCO3− via the Cl−/ HCO3− anion exchanger (AE). Hence, K+ reabsorption by H+/K+-ATPase adds HCO3− ions to the medullary interstitial compartment. ATP, adenosine triphosphate; ADP, adenosine diphosphate; Pi, inorganic phosphate.
Kidney International  , 41-53DOI: ( /j.kint )
Copyright © 2017 International Society of Nephrology Terms and Conditions