These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: ROMK channels are inhibited in the aldosterone-sensitive distal nephron of renal tubule Nedd4-2-deficient mice.
    Author: Zhang DD, Zheng JY, Duan XP, Lin DH, Wang WH.
    Journal: Am J Physiol Renal Physiol; 2022 Jan 01; 322(1):F55-F67. PubMed ID: 34843409.
    Abstract:
    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.
    [Abstract] [Full Text] [Related] [New Search]