Evidence map›Paper›PMID 15858048›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005

Endogenous hydrogen peroxide regulates the excitability of midbrain dopamine neurons via ATP-sensitive potassium channels.

Marat V Avshalumov, Billy T Chen, Tibor Koós, James M Tepper, Margaret E Rice

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

81 citing papers in PubMed, 164 citations in OpenAlex.

  1. Trial
  2. Article
  3. Hydrogen peroxide exposure to bullfrog heart causes ST segment elevation.The Journal of veterinary medical science · 2025
    Article
  4. Article
  5. Article
  6. Sodium butyrate activates the KImmunity, inflammation and disease · 2024
    Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Antioxidants (Basel, Switzerland) · 2022
    Review
  15. Article
  16. Article
  17. Anti-hypertensive effect of hydrogen peroxide acting centrally.Hypertension research : official journal of the Japanese Society of Hypertension · 2020
    Article
  18. Hydrogen Peroxide Gates a Voltage-Dependent Cation Current inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019
    Article
  19. Article
  20. Hydrogen peroxide inhibits neurons in the paraventricular nucleus of the hypothalamus via potassium channel activation.American journal of physiology. Regulatory, integrative and comparative physiology · 2019
    Article

21 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

Marat V AvshalumovDepartment of Neurosurgery, New York University School of Medicine, New York, New York 10016, USA.
Billy T Chen
Tibor Koós
James M Tepper
Margaret E Rice
New York University · USRutgers, The State University of New Jersey · US

Funding

Electrochemical Analysis of Dopamine ReleaseR01NS036362 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI RICE, MARGARET E · 1997 to 2011
$3.3M
Electrochemical Analysis of Dopamine ReleaseR56NS036362 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI RICE, MARGARET E · 2007 to 2007
$423k
Regulation of Dopamine Release by ROSR21NS045325 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI RICE, MARGARET E · 2003 to 2004
$401k
NINDS NIH HHS NS-36362NINDS NIH HHS NS-45325NINDS NIH HHS R01 NS036362NINDS NIH HHS R21 NS045325NINDS NIH HHS R56 NS036362
6 · The paper itself

Abstract

ATP-sensitive K+ (K(ATP)) channels link metabolic state to cell excitability. Here, we examined regulation of K(ATP) channels in substantia nigra dopamine neurons by hydrogen peroxide (H2O2), which is produced in all cells during aerobic metabolism. Blockade of K(ATP) channels by glibenclamide (100 nM) or depletion of intracellular H2O2 by including catalase, a peroxidase enzyme, in the patch pipette increased the spontaneous firing rate of all dopamine neurons tested in guinea pig midbrain slices. Using fluorescence imaging with dichlorofluorescein to visualize intracellular H2O2, we found that moderate increases in H2O2 during partial inhibition of glutathione (GSH) peroxidase by mercaptosuccinate (0.1-0.3 mM) had no effect on dopamine neuron firing rate. However, with greater GSH inhibition (1 mM mercaptosuccinate) or application of exogenous H2O2, 50% of recorded cells showed K(ATP) channel-dependent hyperpolarization. Responsive cells also hyperpolarized with diazoxide, a selective opener for K(ATP) channels containing sulfonylurea receptor SUR1 subunits, but not with cromakalim, a selective opener for SUR2-based channels, indicating that SUR1-based K(ATP) channels conveyed enhanced sensitivity to elevated H2O2. In contrast, when endogenous H2O2 levels were increased after inhibition of catalase, the predominant peroxidase in the substantia nigra, with 3-amino-1,2,4-triazole (1 mM), all dopamine neurons responded with glibenclamide-reversible hyperpolarization. Fluorescence imaging of H2O2 indicated that catalase inhibition rapidly amplified intracellular H2O2, whereas inhibition of GSH peroxidase, a predominantly glial enzyme, caused a slower, smaller increase, especially in nonresponsive cells. Thus, endogenous H2O2 modulates neuronal activity via K(ATP) channel opening, thereby enhancing the reciprocal relationship between metabolism and excitability.

Indexed as

Adenosine TriphosphateAnalysis of VarianceAnimalsCromakalimDiazoxideDopamineDose-Response Relationship, DrugDose-Response Relationship, RadiationDrug InteractionsElectric StimulationGlutathione PeroxidaseGlyburideGuinea PigsHydrogen PeroxideHypoglycemic AgentsIn Vitro Techniques2-thiomalic acidAdenosine TriphosphateCromakalimDiazoxideDopamineGlutathione PeroxidaseGlyburideHydrogen PeroxideHypoglycemic AgentsIsoquinolineslucifer yellowOrganoplatinum CompoundsPotassium ChannelsTetrodotoxinThiomalatestrans-(dichloroamminethiazole)platinum(II)Vasodilator Agents

Identifiers

PMID15858048
PMCPMC6725114
OpenAlexW2007646404

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.