| First Author | Zhang DD | Year | 2022 |
| Journal | Am J Physiol Renal Physiol | Volume | 322 |
| Issue | 1 | Pages | F55-F67 |
| PubMed ID | 34843409 | Mgi Jnum | J:331617 |
| Mgi Id | MGI:7378603 | Doi | 10.1152/ajprenal.00306.2021 |
| Citation | Zhang DD, et al. (2022) ROMK channels are inhibited in the aldosterone-sensitive distal nephron of renal tubule Nedd4-2-deficient mice. Am J Physiol Renal Physiol 322(1):F55-F67 |
| abstractText | We used whole cell recording to examine the renal outer medullary K(+) channel (ROMK or Kir1.1) and epithelial Na(+) channel (ENaC) in the late distal convoluted tubule (DCT2)/initial connecting tubule (iCNT) and in the cortical collecting duct (CCD) of kidney tubule-specific neural precursor cell-expressed developmentally downregulated protein 4-2 (Nedd4-2) knockout mice (Ks-Nedd4-2 KO) and floxed neural precursor cell-expressed developmentally downregulated 4-like (Nedd4l) mice (control). Tertiapin Q (TPNQ)-sensitive K(+) currents (ROMK) were smaller in both the DCT2/iCNT and CCD of Ks-Nedd4-2 KO mice on a normal diet than in control mice. Neither high dietary salt intake nor low dietary salt intake had a significant effect on ROMK activity in the DCT2/iCNT and CCD of control and Ks-Nedd4-2 KO mice. In contrast, high dietary K(+) intake (HK) increased, whereas low dietary K(+) intake (LK) decreased TPNQ-sensitive K(+) currents in floxed Nedd4l mice. However, the effects of dietary K(+) intake on ROMK channel activity were absent in Ks-Nedd4-2 KO mice since neither HK nor LK significantly affected TPNQ-sensitive K(+) currents in the DCT2/iCNT and CCD. Moreover, TPNQ-sensitive K(+) currents in the DCT2/iCNT and CCD of Ks-Nedd4-2 KO mice on HK were similar to those of control mice on LK. Amiloride-sensitive Na(+) currents in the DCT2/iCNT and CCD were significantly higher in Ks-Nedd4-2 KO mice than in floxed Nedd4l mice on a normal K(+) diet. HK increased ENaC activity of the DCT2/iCNT only in control mice, but HK stimulated ENaC of the CCD in both control and Ks-Nedd4-2 KO mice. Moreover, the HK-induced increase in amiloride-sensitive Na(+) currents was larger in Ks-Nedd4-2 KO mice than in control mice. Deletion of Nedd4-2 increased with no lysine kinase 1 expression and abolished HK-induced inhibition of with no lysine kinase 1. We conclude that deletion of Nedd4-2 increases ENaC activity but decreases ROMK activity in the aldosterone-sensitive distal nephron and that HK fails to stimulate ROMK, but robustly increases ENaC activity in the CCD of Nedd4-2-deficient mice.NEW & NOTEWORTHY We demonstrate that renal outer medullary K(+) (ROMK) channel activity is inhibited in the late distal convoluted tubule/initial connecting tubule and cortical collecting duct of neural precursor cell-expressed developmentally downregulated protein 4-2 (Nedd4-2)-deficient mice. Also, deletion of Nedd4-2 abolishes the stimulatory effect of dietary K(+) intake on ROMK. The lack of high K(+)-induced stimulation of ROMK is associated with the absence of high K(+)-induced inhibition of with no lysine kinase 1. |
