Evidence map›Paper›PMID 37707951›Full record

ArticleJCI insight2023

Mice lacking γENaC palmitoylation sites maintain benzamil-sensitive Na+ transport despite reduced channel activity.

Andrew J Nickerson, Stephanie M Mutchler, Shaohu Sheng, Natalie A Cox, Evan C Ray, Ossama B Kashlan, Marcelo D Carattino, Allison L Marciszyn, Aaliyah Winfrey, Sebastien Gingras and 3 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Contribution of murine strain background to NabioRxiv : the preprint server for biology · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Influence of proteolytic cleavage of ENaC's γ subunit upon NaAmerican journal of physiology. Renal physiology · 2024
    Article
  8. Epithelial NaComprehensive Physiology · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Andrew J NickersonDepartment of Medicine.
Stephanie M MutchlerDepartment of Medicine.
Shaohu ShengDepartment of Medicine.
Natalie A CoxDepartment of Medicine.
Evan C RayDepartment of Medicine.
Ossama B KashlanDepartment of Medicine.
Marcelo D CarattinoDepartment of Medicine.
Allison L MarciszynDepartment of Medicine.
Aaliyah WinfreyDepartment of Medicine.
Sebastien GingrasDepartment of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Annet KiraboDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Rebecca P HugheyDepartment of Medicine.
Thomas R KleymanDepartment of Medicine.
University of Pittsburgh · USVanderbilt University Medical Center · US

Funding

Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
T32 Research Training in Diabetes and EndocrinologyT32DK007052 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ROBERT M O'DOHERTY · 1986 to 2026
$6.3M
Resource Development CoreU54DK137329 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Gerard L Apodaca · 2023 to 2026
$4.8M
ENaC regulation and its role in blood pressure homeostasisR01HL147818 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Annet Kirabo, Thomas R Kleyman · 2019 to 2026
$4.6M
Renal and Epithelial Biology Training ProgramT32DK061296 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2002 to 2022
$3.1M
Role of piezo channels in intercalated cellsR01DK129285 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R, SATLIN, LISA M. · 2022 to 2025
$2.3M
ENaC regulation by biliary factorsR01DK125439 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KASHLAN, OSSAMA B · 2020 to 2023
$1.8M
Proteolytic activation of ENaC in Proteinuric Kidney DiseaseK08DK110332 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RAY, EVAN CROSS · 2016 to 2021
$903k
NHLBI NIH HHS R01 HL147818NIDDK NIH HHS K08 DK110332NIDDK NIH HHS P30 DK079307NIDDK NIH HHS R01 DK125439NIDDK NIH HHS R01 DK129285NIDDK NIH HHS T32 DK007052NIDDK NIH HHS T32 DK061296NIDDK NIH HHS U54 DK137329
6 · The paper itself

Abstract

Epithelial Na+ channels (ENaCs) control extracellular fluid volume by facilitating Na+ absorption across transporting epithelia. In vitro studies showed that Cys-palmitoylation of the γENaC subunit is a major regulator of channel activity. We tested whether γ subunit palmitoylation sites are necessary for channel function in vivo by generating mice lacking the palmitoylated cysteines (γC33A,C41A) using CRISPR/Cas9 technology. ENaCs in dissected kidney tubules from γC33A,C41A mice had reduced open probability compared with wild-type (WT) littermates maintained on either standard or Na+-deficient diets. Male mutant mice also had higher aldosterone levels than WT littermates following Na+ restriction. However, γC33A,C41A mice did not have reduced amiloride-sensitive Na+ currents in the distal colon or benzamil-induced natriuresis compared to WT mice. We identified a second, larger conductance cation channel in the distal nephron with biophysical properties distinct from ENaC. The activity of this channel was higher in Na+-restricted γC33A,C41A versus WT mice and was blocked by benzamil, providing a possible compensatory mechanism for reduced prototypic ENaC function. We conclude that γ subunit palmitoylation sites are required for prototypic ENaC activity in vivo but are not necessary for amiloride/benzamil-sensitive Na+ transport in the distal nephron or colon.

Indexed as

AmilorideLipoylationAnimalsEpithelial Sodium ChannelsMaleMiceSodiumAmiloridebenzamilEpithelial Sodium ChannelsSodiumCell BiologyEpithelial transport of ions and waterIon channelsNephrology

Identifiers

PMID37707951
PMCPMC10721255
OpenAlexW4386741861

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.