Evidence map›Paper›PMID 20185796›Full record

ArticleCirculation research2010

A novel mitochondrial K(ATP) channel assay.

Andrew P Wojtovich, David M Williams, Marcin K Karcz, Coeli M B Lopes, Daniel A Gray, Keith W Nehrke, Paul S Brookes

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

31 citing papers in PubMed, 56 citations in OpenAlex.

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  11. Article
  12. Cardiovascular KPathobiology of aging & age related diseases · 2016
    Review
  13. KATP Channels in the Cardiovascular System.Physiological reviews · 2016
    Review
  14. A highly selective mitochondria-targeting fluorescent K(+) sensor.Angewandte Chemie (International ed. in English) · 2015
    Article
  15. Article
  16. Article
  17. Review
  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

7 authors at 1 institution in 1 country.

Andrew P WojtovichDepartment of Pharmacology, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA.
David M Williams
Marcin K Karcz
Coeli M B Lopes
Daniel A Gray
Keith W Nehrke
Paul S Brookes
Unity Health System · US

Funding

SIRT1, Nitro-Lipids and CardioprotectionR01HL071158 · NHLBI · UNIVERSITY OF ROCHESTER · PI BROOKES, PAUL S · 2003 to 2025
$7.7M
Mitochondrial K+ Channels and CardioprotectionR01GM087483 · NIGMS · UNIVERSITY OF ROCHESTER · PI BROOKES, PAUL S, NEHRKE, KEITH · 2010 to 2017
$2.3M
NHLBI NIH HHS R01 HL071158NHLBI NIH HHS R01-HL071158NIGMS NIH HHS R01 GM087483NIGMS NIH HHS R01-GM-087483
6 · The paper itself

Abstract

rationaleThe mitochondrial ATP sensitive potassium channel (mK(ATP)) is implicated in cardioprotection by ischemic preconditioning (IPC), but the molecular identity of the channel remains controversial. The validity of current methods to assay mK(ATP) activity is disputed.

objectiveWe sought to develop novel methods to assay mK(ATP) activity and its regulation. METHODS AND

resultsUsing a thallium (Tl(+))-sensitive fluorophore, we developed a novel Tl(+) flux based assay for mK(ATP) activity, and used this assay probe several aspects of mK(ATP) function. The following key observations were made. (1) Time-dependent run down of mK(ATP) activity was reversed by phosphatidylinositol-4,5-bisphosphate (PIP(2)). (2) Dose responses of mK(ATP) to nucleotides revealed a UDP EC(50) of approximately 20 micromol/L and an ATP IC(50) of approximately 5 micromol/L. (3) The antidepressant fluoxetine (Prozac) inhibited mK(ATP) (IC(50)=2.4 micromol/L). Fluoxetine also blocked cardioprotection triggered by IPC, but did not block protection triggered by a mK(ATP)-independent stimulus. The related antidepressant zimelidine was without effect on either mK(ATP) or IPC.

conclusionsThe Tl(+) flux mK(ATP) assay was validated by correlation with a classical mK(ATP) channel osmotic swelling assay (R(2)=0.855). The pharmacological profile of mK(ATP) (response to ATP, UDP, PIP(2), and fluoxetine) is consistent with that of an inward rectifying K(+) channel (K(IR)) and is somewhat closer to that of the K(IR)6.2 than the K(IR)6.1 isoform. The effect of fluoxetine on mK(ATP)-dependent cardioprotection has implications for the growing use of antidepressants in patients who may benefit from preconditioning.

Indexed as

Spectrometry, FluorescenceAdenosine TriphosphateAnimalsAntidepressive Agents, Second-GenerationBenzothiazolesBiological AssayCoumarinsFluorescent DyesFluoxetineGlycineIn Vitro TechniquesIschemic Preconditioning, MyocardialKineticsMaleMitochondria, HeartMitochondrial SwellingAdenosine TriphosphateAntidepressive Agents, Second-GenerationBenzothiazolesCoumarinsFluorescent DyesFluoxetineGlycinemitochondrial K(ATP) channelN-(3-(2-benzothiazolyl)-6-(2-(2-(bis(carboxymethyl)amino)-5-methylphenoxy)ethoxy)-2-oxo-2H-1-benzopyran-7-yl)-N-(carboxymethyl)glycinePhosphatidylinositol 4,5-DiphosphatePotassiumPotassium ChannelsThalliumUridine Diphosphate

Identifiers

PMID20185796
PMCPMC2857559
OpenAlexW1970672273

What OpenQuestion holds

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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.