Evidence map›Paper›PMID 24935944›Full record

ArticleHypertension (Dallas, Tex. : 1979)2014

HV1 acts as a sodium sensor and promotes superoxide production in medullary thick ascending limb of Dahl salt-sensitive rats.

Chunhua Jin, Jingping Sun, Carly A Stilphen, Susan M E Smith, Hiram Ocasio, Brent Bermingham, Sandip Darji, Avirup Guha, Roshan Patel, Aron M Geurts and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Hv1 channel in immune cells and pharmacology.Pharmacological research · 2025
    Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Oral NaHCOJournal of immunology (Baltimore, Md. : 1950) · 2018
    Article
  10. Voltage and pH sensing by the voltage-gated proton channel, HJournal of the Royal Society, Interface · 2018
    Review
  11. Involvement of ENaC in the development of salt-sensitive hypertension.American journal of physiology. Renal physiology · 2017
    Review
  12. Review
  13. Proton channels and renal hypertensive injury: a key piece of the Dahl salt-sensitive rat puzzle?American journal of physiology. Regulatory, integrative and comparative physiology · 2016
    Review
  14. Review
  15. 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 1 institution in 1 country.

Chunhua JinFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.).
Jingping SunFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.).
Carly A StilphenFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.).
Susan M E SmithFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.).
Hiram OcasioFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.).
Brent BerminghamFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.).
Sandip DarjiFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.).
Avirup GuhaFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.).
Roshan PatelFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.).
Aron M GeurtsFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.).
Howard J JacobFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.).
Nevin A LambertFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.).
Paul M O'ConnorFrom the Department of Physiology (C.J, J.S., C.A.S., H.O., B.B., S.D., A.G., R.P., P.M.O.) and Department of Pharmacology and Toxicology (N.A.L.), Georgia Regents University, Augusta; Department of Physiology, Medical College of Wisconsin, Milwaukee (A.M.G., H.J.J.); and Department of Biology & Physics, Kennesaw State University, Atlanta, GA (S.M.E.S.). paoconnor@gru.edu.
Medical College of Wisconsin · US

Funding

Mechanistic characterization of genes for hypertension and renal disease.RC2HL101681 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI JACOB, HOWARD J · 2009 to 2010
$6.6M
GPCR signaling complexes in living cellsR01GM078319 · NIGMS · AUGUSTA UNIVERSITY · PI LAMBERT, NEVIN ALAN · 2007 to 2017
$2.1M
Role of HV1 in development of salt-sensitive hypertension and renal injuryR01DK099548 · NIDDK · AUGUSTA UNIVERSITY · PI O'CONNOR, PAUL MICHAEL · 2014 to 2018
$1.6M
NHLBI NIH HHS RC2 HL101681NIDDK NIH HHS R01 DK099548NIGMS NIH HHS GM078319NIGMS NIH HHS R01 GM078319
6 · The paper itself

Abstract

We previously characterized a H(+) transport pathway in medullary thick ascending limb nephron segments that when activated stimulated the production of superoxide by nicotinamide adenine dinucleotide phosphate oxidase. Importantly, the activity of this pathway was greater in Dahl salt-sensitive rats than salt-resistant (SS.13(BN)) rats, and superoxide production was enhanced in low Na(+) media. The goal of this study was to determine the molecular identity of this pathway and its relationship to Na(+). We hypothesized that the voltage-gated proton channel, HV1, was the source of superoxide-stimulating H(+) currents. To test this hypothesis, we developed HV1(-/-) null mutant rats on the Dahl salt-sensitive rat genetic background using zinc-finger nuclease gene targeting. HV1 could be detected in medullary thick limb from wild-type rats. Intracellular acidification using an NH4Cl prepulse in 0 sodium/BaCl2 containing media resulted in superoxide production in thick limb from wild-type but not HV1(-/-) rats (P<0.05) and more rapid recovery of intracellular pH in wild-type rats (ΔpHI 0.005 versus 0.002 U/s, P=0.046, respectively). Superoxide production was enhanced by low intracellular sodium (<10 mmol/L) in both thick limb and peritoneal macrophages only when HV1 was present. When fed a high-salt diet, blood pressure, outer medullary renal injury (tubular casts), and oxidative stress (4-hydroxynonenal staining) were significantly reduced in HV1(-/-) rats compared with wild-type Dahl salt-sensitive rats. We conclude that HV1 is expressed in medullary thick ascending limb and promotes superoxide production in this segment when intracellular Na(+) is low. HV1 contributes to the development of hypertension and renal disease in Dahl salt-sensitive rats.

Indexed as

AnimalsDisease Models, AnimalHydrogenHydrogen-Ion ConcentrationHypertensionIon ChannelsKidney DiseasesLoop of HenleMaleNADPPatch-Clamp TechniquesRatsRats, Inbred DahlRats, Mutant StrainsReactive Oxygen SpeciesSodiumHv1 proton channel, ratHydrogenIon ChannelsNADPReactive Oxygen SpeciesSodiumSuperoxidesfree radicalshypertensionoxidative stress

Identifiers

PMID24935944
PMCPMC4324599
OpenAlexW2094977963

What OpenQuestion holds

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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.