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Abstract: SA-PO1041

Depletion of Kidney-Specific WNK1 (KS-WNK1) Abolishes the Effect of High Dietary K Intake (HK) on ROMK Channel in the Distal Convoluted Tubule (DCT)

Session Information

  • Na+, K+, Cl-
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Fluid, Electrolytes, and Acid-Base

  • 703 Na+, K+, Cl- Basic


  • Wang, WenHui, New York Medical College, Valhalla, New York, United States
  • Wu, Peng, New York Medical College, Valhalla, New York, United States
  • Su, Xiao-Tong, New York Medical College, Valhalla, New York, United States
  • Terker, Andrew, OHSU, Portland, Oregon, United States
  • Gao, Zhongxiuzi, New York Medical College, Valhalla, New York, United States
  • Ellison, David H., Oregon Health & Science University , Portland, Oregon, United States
  • Hadchouel, Juliette, INSERM, Paris, France
  • Teulon, Jacques, University Pierre et Marie Curie-UPMC, Paris, France

Previous studies have shown that with-no-lysine kinases (WNK) regulate ROMK (Kir1.1) channel, a K secretory channel expressed in the apical membrane of aldosterone-sensitive distal nephron (ASDN). While WNK4 and full-length WNK1 (L-WNK1) inhibit ROMK cannel activity by facilitating endocytosis, KS-WNK has been shown to inhibit L-WNK1 thereby stimulating ROMK.


Since KS-WNK1 is mainly expressed in the DCT, we now performed the whole-cell patch-clamp recording to measure TPNQ (ROMK inhibitor)-sensitive K currents in the isolated split-open DCT of WT and WNK4 knockout (KO) or KS-WNK1 KO mice.


TPNQ-sensitive K currents in DCT2 of KS-WNK1 KO (450±40 pA) and WNK4 KO mice (370±50 pA) were significantly smaller than that of WT mice (1060±120 pA). Moreover, WNK4 KO mice were hypokalemic (3.2±0.05 mM) while KS-WNK1 KO mice had normal plasma K level (4.5±0.3 mM). Thus, it is possible that diminished ROMK cannel activity in WNK4 KO mice may be the result of hypokalemia. HK intake (7 days) significantly increased K currents in DCT2 to 1600±80 pA (WT) and to 1090±40 pA (WNK4 KO), suggesting that lack of WNK4 did not compromise the effect of HK intake on ROMK in DCT2. In contrast, HK intake fails to stimulate ROMK channels in DCT of KS-WNK1 KO mice because TPNQ-sensitive K currents were not significantly increased (540±30 pA) in DCT2 of KS-WNK1 KO mice. However, plasma K level in KS-WNK1 KO mice on HK was even lower (3.9±0.1 mM) than that of WT mice (4.4±0.1 mM), suggesting that defective regulation of ROMK by HK in DCT2 did not decrease net renal K excretion in KS-WNK1 KO mice. This notion is supported by the observation that HK intake actually stimulates TPNQ-sensitive K currents in the CCD from 1090±90 pA to 2400±140 pA in KS-WNK1 KO mice.


In summary, ROMK cannel activity is decreased in DCT2 of WNK4 KO and KS-WNK1 KO mice. However, only the depletion of KS-WNK1 but not WNK4 abolished the stimulatory effect of HK intake on ROMK in DCT2. However, HK intake is still able to activate ROMK in the CCD of KS-WNK1 KO mice. We conclude that KS-WNK1 plays a role in mediating the stimulatory effect of HK intake on ROMK in the DCT2 but not in the CCD.


  • NIDDK Support