Evidence map›Paper›PMID 25298526›Full record

ArticleAmerican journal of physiology. Renal physiology2014

Local pH domains regulate NHE3-mediated Na⁺ reabsorption in the renal proximal tubule.

Jens Christian Brasen, James L Burford, Alicia A McDonough, Niels-Henrik Holstein-Rathlou, Janos Peti-Peterdi

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Renal physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

32 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
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  9. High dietary KAmerican journal of physiology. Renal physiology · 2023
    Article
  10. Article
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  14. A role for tubular NaAmerican journal of physiology. Renal physiology · 2020
    Article
  15. Sex differences in solute transport along the nephrons: effects of NaAmerican journal of physiology. Renal physiology · 2020
    Article
  16. Article
  17. Article
  18. Article
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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

5 authors at 3 institutions in 2 countries.

Jens Christian BrasenDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; Biomedical Engineering, Department of Electrical Engineering, Technical University of Denmark, Lyngby, Denmark; and jcbrasen@sund.ku.dk.
James L BurfordDepartments of Physiology and Biophysics and Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California; and.
Alicia A McDonoughDepartment of Cell and Neurobiology, University of Southern California, Los Angeles, California.
Niels-Henrik Holstein-RathlouDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark;
Janos Peti-PeterdiDepartments of Physiology and Biophysics and Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California; and.
University of Southern California · USTechnical University of Denmark · DKUniversity of Copenhagen · DK

Funding

Multiphoton Imaging of the Juxtaglomerular ApparatusR01DK064324 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JANOS PETI-PETERDI · 2004 to 2026
$8.4M
Sodium transporter regulation during hypertensionR01DK083785 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI AURELIE EDWARDS, Alicia A. McDonough · 2011 to 2026
$5.8M
Sodium-chloride co-transporter regulation in the kidneyR56DK083785 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MCDONOUGH, ALICIA A., YU, ALAN S · 2010 to 2010
$173k
NIDDK NIH HHS DK-083785NIDDK NIH HHS DK-64324NIDDK NIH HHS R01 DK083785
6 · The paper itself

Abstract

The proximal tubule Na(+)/H(+) exchanger 3 (NHE3), located in the apical dense microvilli (brush border), plays a major role in the reabsorption of NaCl and water in the renal proximal tubule. In response to a rise in blood pressure NHE3 redistributes in the plane of the plasma membrane to the base of the brush border, where NHE3 activity is reduced. This NHE3 redistribution is assumed to provoke pressure natriuresis; however, it is unclear how NHE3 redistribution per se reduces NHE3 activity. To investigate if the distribution of NHE3 in the brush border can change the reabsorption rate, we constructed a spatiotemporal mathematical model of NHE3-mediated Na(+) reabsorption across a proximal tubule cell and compared the model results with in vivo experiments in rats. The model predicts that when NHE3 is localized exclusively at the base of the brush border, it creates local pH microdomains that reduce NHE3 activity by >30%. We tested the model's prediction experimentally: the rat kidney cortex was loaded with the pH-sensitive fluorescent dye BCECF, and cells of the proximal tubule were imaged in vivo using confocal fluorescence microscopy before and after an increase of blood pressure by ∼50 mmHg. The experimental results supported the model by demonstrating that a rise of blood pressure induces the development of pH microdomains near the bottom of the brush border. These local changes in pH reduce NHE3 activity, which may explain the pressure natriuresis response to NHE3 redistribution.

Indexed as

AnimalsBlood PressureCarbonic AnhydrasesCytosolHydrogen-Ion ConcentrationHypertension, RenalKidney Tubules, ProximalMaleMicrovilliRatsRats, Sprague-DawleySodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSodium-Potassium-Exchanging ATPaseCarbonic AnhydrasesSlc9a3 protein, ratSodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSodium-Potassium-Exchanging ATPaseintravital confocal microscopyNa+/H+ exchanger 3pressure natriuresisproximal tubulespatiotemporal mathematical model

Identifiers

PMID25298526
PMCPMC4254968
OpenAlexW2055790786

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.