Pendrin-null mice develop severe hypokalemia following dietary Na<sup>+</sup> and K<sup>+</sup> restriction: role of ENaC.

Details

Serval ID
serval:BIB_12D5038359C4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pendrin-null mice develop severe hypokalemia following dietary Na<sup>+</sup> and K<sup>+</sup> restriction: role of ENaC.
Journal
American journal of physiology. Renal physiology
Author(s)
Pham T.D., Elengickal A.J., Verlander J.W., Al-Qusairi L., Chen C., Abood D.C., King S.A., Loffing J., Welling P.A., Wall S.M.
ISSN
1522-1466 (Electronic)
ISSN-L
1522-1466
Publication state
Published
Issued date
01/05/2022
Peer-reviewed
Oui
Volume
322
Number
5
Pages
F486-F497
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Abstract
Pendrin is an intercalated cell Cl <sup>-</sup> /[Formula: see text] exchanger thought to participate in K <sup>+</sup> -sparing NaCl absorption. However, its role in K <sup>+</sup> homeostasis has not been clearly defined. We hypothesized that pendrin-null mice will develop hypokalemia with dietary K <sup>+</sup> restriction. We further hypothesized that pendrin knockout (KO) mice mitigate urinary K <sup>+</sup> loss by downregulating the epithelial Na <sup>+</sup> channel (ENaC). Thus, we examined the role of ENaC in Na <sup>+</sup> and K <sup>+</sup> balance in pendrin KO and wild-type mice following dietary K <sup>+</sup> restriction. To do so, we examined the relationship between Na <sup>+</sup> and K <sup>+</sup> balance and ENaC subunit abundance in K <sup>+</sup> -restricted pendrin-null and wild-type mice that were NaCl restricted or replete. Following a NaCl-replete, K <sup>+</sup> -restricted diet, K <sup>+</sup> balance and serum K <sup>+</sup> were similar in both groups. However, following a Na <sup>+</sup> , K <sup>+</sup> , and Cl <sup>-</sup> -deficient diet, pendrin KO mice developed hypokalemia from increased K <sup>+</sup> excretion. The fall in serum K <sup>+</sup> observed in K <sup>+</sup> -restricted pendrin KO mice was enhanced with ENaC stimulation but eliminated with ENaC inhibition. The fall in serum K <sup>+</sup> observed in K <sup>+</sup> -restricted pendrin KO mice was enhanced with ENaC stimulation but eliminated with ENaC inhibition. However, reducing ENaC activity also reduced blood pressure and increased apparent intravascular volume contraction, since KO mice had lower serum Na <sup>+</sup> , higher blood urea nitrogen and hemoglobin, greater weight loss, greater metabolic alkalosis, and greater NaCl excretion. We conclude that dietary Na <sup>+</sup> and K <sup>+</sup> restriction induces hypokalemia in pendrin KO mice. Pendrin-null mice limit renal K <sup>+</sup> loss by downregulating ENaC. However, this ENaC downregulation occurs at the expense of intravascular volume.NEW & NOTEWORTHY Pendrin is an apical Cl <sup>-</sup> /[Formula: see text] exchanger that provides renal K <sup>+</sup> -sparing NaCl absorption. The pendrin-null kidney has an inability to fully conserve K <sup>+</sup> and limits renal K <sup>+</sup> loss by downregulating the epithelial Na <sup>+</sup> channel (ENaC). However, with Na <sup>+</sup> restriction, the need to reduce ENaC for K <sup>+</sup> balance conflicts with the need to stimulate ENaC for intravascular volume. Therefore, NaCl restriction stimulates ENaC less in pendrin-null mice than in wild-type mice, which mitigates their kaliuresis and hypokalemia but exacerbates volume contraction.
Keywords
Animals, Anion Transport Proteins/metabolism, Diet, Epithelial Sodium Channels/metabolism, Hypokalemia, Mice, Mice, Knockout, epithelial Na+ channel, pendrin, potassium
Pubmed
Web of science
Create date
07/03/2022 11:14
Last modification date
04/11/2023 7:07
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