| First Author | Wu P | Year | 2018 |
| Journal | Am J Physiol Renal Physiol | Volume | 315 |
| Issue | 2 | Pages | F223-F230 |
| PubMed ID | 29667910 | Mgi Jnum | J:281418 |
| Mgi Id | MGI:6367854 | Doi | 10.1152/ajprenal.00050.2018 |
| Citation | Wu P, et al. (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. Am J Physiol Renal Physiol 315(2):F223-F230 |
| abstractText | 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. |
