Abstract
Clinically, potassium supplementation has been shown to lower blood pressure and reduce the risk of stroke through modulation of potassium excretion and sodium reabsorption. Hypokalemia activates the renal sodium chloride cotransporter (NCC) along the distal convoluted tubule (DCT), at least in part, through with-no-lysine 4 (WNK4) kinase and STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) signaling. The DCT also expresses a kinase-deficient, kidney-specific form of WNK1 (KS-WNK1), but its role in NCC activation is unclear. In this issue of the JCI, Boyd-Shiwarski and colleagues found that KS-WNK1 enhanced the effects of potassium on NCC activation in vivo. Specifically, they showed that mice lacking KS-WNK1 did not respond as robustly to dietary challenge. Additionally, in vivo expression of a mutated KS-WNK1 disrupted WNK body, or biomolecular condensate, formation and renal function. These findings, along with those of previous studies, indicate that KS-WNK1 may regulate potassium homeostasis by increasing the kidney's sensitivity to salt-dependent stress.