Evidence map›Paper›PMID 27555660›Full record

ArticleScience signaling2016

Dynamic DNA methylation regulates neuronal intrinsic membrane excitability.

Jarrod P Meadows, Mikael C Guzman-Karlsson, Scott Phillips, Jordan A Brown, Sarah K Strange, J David Sweatt, John J Hablitz

Open access · greenAbstract read
In one paragraph

Article in Science signaling, 2016. 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
4.9field-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

32 citing papers in PubMed, 60 citations in OpenAlex.

  1. DNA Methylation in Long-Term Memory.Physiology (Bethesda, Md.) · 2025
    Review
  2. Article
  3. Article
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  5. Article
  6. The computational power of the human brain.Frontiers in cellular neuroscience · 2023
    Review
  7. Article
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  9. 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 2 institutions in 1 country.

Jarrod P MeadowsDepartment of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Mikael C Guzman-KarlssonDepartment of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Scott PhillipsDepartment of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Jordan A BrownDepartment of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Sarah K StrangeDepartment of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J David SweattDepartment of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
John J HablitzDepartment of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA. jhablitz@uab.edu.
University of Alabama at Birmingham · USCivitan International · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM008361 · NIGMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI YACOUBIAN, TALENE ALENE · 1992 to 2024
$16.8M
Biochemical Mechanisms of Neural PlasticityR01MH057014 · NIMH · VANDERBILT UNIVERSITY · PI WINDER, DANNY G. · 1996 to 2019
$9.3M
UAB Neuroscience Core CenterP30NS047466 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI STANDAERT, DAVID G. · 2005 to 2019
$8.5M
UAB Research Training Program in Neurobiology of Cognition and Cognitive DisordersT32NS061788 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Farah Dominique Lubin · 2008 to 2026
$4.5M
NIGMS NIH HHS T32 GM008361NIMH NIH HHS R01 MH057014NINDS NIH HHS P30 NS047466NINDS NIH HHS T32 NS061788
6 · The paper itself

Abstract

Epigenetic modifications, such as DNA cytosine methylation, contribute to the mechanisms underlying learning and memory by coordinating adaptive gene expression and neuronal plasticity. Transcription-dependent plasticity regulated by DNA methylation includes synaptic plasticity and homeostatic synaptic scaling. Memory-related plasticity also includes alterations in intrinsic membrane excitability mediated by changes in the abundance or activity of ion channels in the plasma membrane, which sets the threshold for action potential generation. We found that prolonged inhibition of DNA methyltransferase (DNMT) activity increased intrinsic membrane excitability of cultured cortical pyramidal neurons. Knockdown of the cytosine demethylase TET1 or inhibition of RNA polymerase blocked the increased membrane excitability caused by DNMT inhibition, suggesting that this effect was mediated by subsequent cytosine demethylation and de novo transcription. Prolonged DNMT inhibition blunted the medium component of the after-hyperpolarization potential, an effect that would increase neuronal excitability, and was associated with reduced expression of the genes encoding small-conductance Ca(2+)-activated K(+) (SK) channels. Furthermore, the specific SK channel blocker apamin increased neuronal excitability but was ineffective after DNMT inhibition. Our results suggested that DNMT inhibition enables transcriptional changes that culminate in decreased expression of SK channel-encoding genes and decreased activity of SK channels, thus providing a mechanism for the regulation of neuronal intrinsic membrane excitability by dynamic DNA cytosine methylation. This study has implications for human neurological and psychiatric diseases associated with dysregulated intrinsic excitability.

Indexed as

AnimalsApaminCell LineDNA MethylationEpigenesis, GeneticHumansMembrane PotentialsPyramidal CellsRatsSmall-Conductance Calcium-Activated Potassium ChannelsApaminSmall-Conductance Calcium-Activated Potassium Channels

Identifiers

PMID27555660
PMCPMC5709999
OpenAlexW2510223785

What OpenQuestion holds

Textmetadata
LicenceTDM
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.