Evidence map›Paper›PMID 16260839›Full record

ArticleThe Journal of general physiology2005

Charge screening by internal pH and polyvalent cations as a mechanism for activation, inhibition, and rundown of TRPM7/MIC channels.

J Ashot Kozak, Masayuki Matsushita, Angus C Nairn, Michael D Cahalan

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in The Journal of general physiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

84 citing papers in PubMed, 131 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. TRPM channels in health and disease.Nature reviews. Nephrology · 2024
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. CaInternational journal of molecular sciences · 2022
    Review
  11. Structural mechanism of TRPM7 channel regulation by intracellular magnesium.Cellular and molecular life sciences : CMLS · 2022
    Article
  12. Review
  13. Review
  14. Article
  15. TRPM7-Mediated Calcium Transport in HAT-7 Ameloblasts.International journal of molecular sciences · 2021
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

24 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

4 authors at 3 institutions in 2 countries.

J Ashot KozakDepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697, USA.
Masayuki Matsushita
Angus C Nairn
Michael D Cahalan
University of California, Irvine · USOkayama University · JPYale University · US

Funding

Molecular Mechanisms of lon Channels in T LymphocytesR01NS014609 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CAHALAN, MICHAEL D · 1985 to 2022
$7.0M
Molecular Mechanisms of Ion Channels in T LymphocytesR37NS014609 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CAHALAN, MICHAEL D · 2006 to 2012
$3.3M
Molecular Mechanisms of lon Channels in T LymphocytesR56NS014609 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CAHALAN, MICHAEL D · 2018 to 2018
$514k
NINDS NIH HHS NS14609NINDS NIH HHS R01 NS014609NINDS NIH HHS R37 NS014609NINDS NIH HHS R56 NS014609
6 · The paper itself

Abstract

The Mg2+-inhibited cation (MIC) current, believed to represent activity of TRPM7 channels, is found in lymphocytes and mast cells, cardiac and smooth muscle, and several other eukaryotic cell types. MIC current is activated during whole-cell dialysis with divalent-free internal solutions. Millimolar concentrations of intracellular Mg2+ (or other divalent metal cations) inhibit the channels in a voltage-independent manner. The nature of divalent inhibition and the mechanism of channel activation in an intact cell remain unknown. We show that the polyamines (spermine, spermidine, and putrescine) inhibit the MIC current, also in a voltage-independent manner, with a potency that parallels the number of charges. Neomycin and poly-lysine also potently inhibited MIC current in the absence of Mg2+. These same positively charged ions inhibited IRK1 current in parallel with MIC current, suggesting that they probably act by screening the head group phosphates on PIP2 and other membrane phospholipids. In agreement with this hypothesis, internal protons also inhibited MIC current. By contrast, tetramethylammonium, tetraethylammonium, and hexamethonium produced voltage-dependent block but no inhibition. We show that inhibition by internal polyvalent cations can be relieved by alkalinizing the cytosol using externally applied ammonium or by increasing pH in inside-out patches. Furthermore, in perforated-patch and cell-attached recordings, when intracellular Mg2+ is not depleted, endogenous MIC or recombinant TRPM7 currents are activated by cytosolic alkalinization and inhibited by acidification; and they can be reactivated by PIP2 following rundown in inside-out patches. We propose that MIC (TRPM7) channels are regulated by a charge screening mechanism and may function as sensors of intracellular pH.

Indexed as

Hydrogen-Ion ConcentrationAnimalsCationsCHO CellsCricetinaeCytosolMagnesiumMembrane PotentialsPatch-Clamp TechniquesPhosphatidylinositol 4,5-DiphosphatePhospholipidsPolyaminesPotassium Channels, Inwardly RectifyingRecombinant Fusion ProteinsSecond Messenger SystemsTransfectionCationsMagnesiumPhosphatidylinositol 4,5-DiphosphatePhospholipidsPolyaminesPotassium Channels, Inwardly RectifyingRecombinant Fusion ProteinsTrpm7 protein, mouseTRPM Cation Channels

Identifiers

PMID16260839
PMCPMC2266608
OpenAlexW2153344780

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.