KCNJ10 and Hypokalemia: For example, in hypokalemia, increased Kir4.1/5.1 activity hyperpolarizes cell membranes, drives intracellular Cl− efflux, causes low Cl− levels in epithelial cells, further activates WNK, activates NCC through the phosphorylation of SPAK, increases sodium reabsorption in the DCT, reduces K+ excretion in distal tubules and collecting ducts, and maintains blood potassium levels.