Role of WNK4 and kidney-specific WNK1 in mediating the effect of high dietary K + intake on ROMK channel in the distal convoluted tubule - Archive ouverte HAL
Article Dans Une Revue American Journal of Physiology. Renal Physiology Année : 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

Résumé

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 tertiapin-Q (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 + levels. 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.

Dates et versions

hal-03832902 , version 1 (28-10-2022)

Identifiants

Citer

Peng Wu, Zhong-Xiuzi Gao, Xiao-Tong Su, David H Ellison, Juliette Hadchouel, et al.. 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, 2018, 315 (2), pp.F223-F230. ⟨10.1152/ajprenal.00050.2018⟩. ⟨hal-03832902⟩
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