NYMC Faculty Publications
Role of WNK4 and kidney-specific WNK1 in mediating the effect of high dietary K+ intake on ROMK channel in the distal convoluted tubule
DOI
10.1152/ajprenal.00050.2018
Journal Title
American Journal of Physiology.Renal Physiology
First Page
F223
Last Page
F230
Document Type
Article
Publication Date
August 2018
Department
Pharmacology
Keywords
Hyperkalemia, Hypokalemia, Kidney Tubules, Distal, Potassium, Dietary, K excretion, Kir1.1, Kir4.1 hypokalemia
Disciplines
Medicine and Health Sciences
Abstract
With-no-lysine kinase 4 (WNK4) and kidney-Specific (KS)-WNK1 regulate ROMK (Kir1.1) channels in a variety of cell models. We now explore the role of WNK4 and KS-WNK1 in regulating ROMK in the native distal convoluted tubule (DCT)/connecting tubule (CNT) by measuring TPNQ (ROMK inhibitor)-sensitive K+ currents with whole-cell recording. TPNQ-sensitive K+ currents in DCT2/CNT of KS-WNK1-/- and WNK4-/- mice were significantly smaller than that of WT mice. In contrast, the basolateral K+ channels (a Kir4.1/5.1 heterotetramer) in the DCT were not inhibited. Moreover, WNK4-/- mice were hypokalemic while KS-WNK1-/- mice had normal plasma K+ level. High K+ (HK) intake significantly increased TPNQ-sensitive K+ currents in DCT2/CNT of WT and WNK4-/- mice but not in KS-WNK1-/- mice. However, TPNQ-sensitive K+ currents in the cortical collecting duct (CCD) were normal not only under control conditions but also significantly increased in response to HK in KS-WNK1-/- mice. This suggests that the deletion of KS-WNK1-induced inhibition of ROMK occurs only in the DCT2/CNT. Renal clearance study further demonstrated that the deletion of KS-WNK1 did not affect the renal ability of K+ excretion under control conditions and during increasing K+ intake. Also, HK intake did not cause hyperkalemia in KS-WNK1-/- mice. We conclude that KS-WNK1 but not WNK4 is required for HK-intake-induced stimulation of ROMK activity in DCT2/CNT. However, KS-WNK1 is not essential for HK-induced stimulation of ROMK in the CCD and the lack of KS-WNK1 does not affect net renal K+ excretion.
Recommended Citation
Wu, P., Gao, Z., Su, X., Ellison, D., Hadchouel, J., Teulon, J., & Wang, W. (2018). Role of WNK4 and kidney-specific WNK1 in mediating the effect of high dietary K+ intake on ROMK channel in the distal convoluted tubule. American Journal of Physiology.Renal Physiology, 315 (2), F223-F230. https://doi.org/10.1152/ajprenal.00050.2018
