Evidence map›Paper›PMID 31222975›Full record

ArticlePhysiological reports2019

The sigma-1 receptor behaves as an atypical auxiliary subunit to modulate the functional characteristics of Kv1.2 channels expressed in HEK293 cells.

Madelyn J Abraham, Kayla L Fleming, Sophie Raymond, Adrian Y C Wong, Richard Bergeron

Open access · goldAbstract read
In one paragraph

Article in Physiological reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

  1. Competitive modulation of KFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. A NovelInternational journal of molecular sciences · 2021
    Article
  7. Regulation of KMembranes · 2021
    Article
  8. Article
  9. Article
  10. An ion channel in the company of a transporter.The Journal of general physiology · 2020
    Article
  11. Review
  12. Article
  13. 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

5 authors at 2 institutions in 1 country.

Madelyn J AbrahamDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Kayla L FlemingDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Sophie RaymondNeuroscience, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Adrian Y C WongNeuroscience, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Richard BergeronDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.ORCID 0000-0002-5632-750X
University of Ottawa · CAOttawa Hospital · CA

Funding

CIHR CIHR # PJT-156089
6 · The paper itself

Abstract

Expression of Kv1.2 within Kv1.x potassium channel complexes is critical in maintaining appropriate neuronal excitability and determining the threshold for action potential firing. This is attributed to the interaction of Kv1.2 with a hitherto unidentified protein that confers bimodal channel activation gating, allowing neurons to adapt to repetitive trains of stimulation and protecting against hyperexcitability. One potential protein candidate is the sigma-1 receptor (Sig-1R), which regulates other members of the Kv1.x channel family; however, the biophysical nature of the interaction between Sig-1R and Kv1.2 has not been elucidated. We hypothesized that Sig-1R may regulate Kv1.2 and may further act as the unidentified modulator of Kv1.2 activation. In transiently transfected HEK293 cells, we found that ligand activation of the Sig-1R modulates Kv1.2 current amplitude. More importantly, Sig-1R interacts with Kv1.2 in baseline conditions to influence bimodal activation gating. These effects are abolished in the presence of the auxiliary subunit Kvβ2 and when the Sig-1R mutation underlying ALS16 (Sig-1R-E102Q), is expressed. These data suggest that Kvβ2 occludes the interaction of Sig-1R with Kv1.2, and that E102 may be a residue critical for Sig-1R modulation of Kv1.2. The results of this investigation describe an important new role for Sig-1R in the regulation of neuronal excitability and introduce a novel mechanism of pathophysiology in Sig-1R dysfunction.

Indexed as

Cells, CulturedElectrophysiological PhenomenaHEK293 CellsHumansIon Channel GatingKv1.2 Potassium ChannelPatch-Clamp TechniquesPhenazocineReceptors, sigmaShaker Superfamily of Potassium ChannelsSigma-1 ReceptorKCNAB2 protein, humanKv1.2 Potassium ChannelPhenazocineReceptors, sigmaShaker Superfamily of Potassium ChannelsSigma-1 ReceptorSK&F 10047apFRETion channel biophysicsKvβ subunitmotor neuron diseasevoltage-clamp electrophysiology

Identifiers

PMID31222975
PMCPMC6586770
OpenAlexW2949254508

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.