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Record W2788934158 · doi:10.1016/j.celrep.2018.01.073

BK Potassium Channels Suppress Cavα2δ Subunit Function to Reduce Inflammatory and Neuropathic Pain

2018· article· en· W2788934158 on OpenAlexafffund
Fang‐Xiong Zhang, Vinícius M. Gadotti, Ivana A. Souza, Lina Chen, Gerald W. Zamponi

Bibliographic record

VenueCell Reports · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicIon channel regulation and function
Canadian institutionsAlberta Children's HospitalUniversity of Calgary
FundersNatural Sciences and Engineering Research Council of CanadaCanada Research ChairsCanadian Institutes of Health ResearchAlberta Innovates - Health SolutionsSavoy Foundation
KeywordsDorsal root ganglionBK channelCalcium-activated potassium channelProtein subunitNeuropathic painPotassium channelNeurotransmissionCell biologyDownregulation and upregulationChemistryCalcium channelN-type calcium channelR-type calcium channelExtracellularCalciumNeuroscienceBiophysicsT-type calcium channelBiologyReceptorBiochemistrySpinal cord

Abstract

fetched live from OpenAlex

Cavα2δ subunits contribute to the cell-surface expression of Cav2 calcium channels. Upregulation of Cavα2δ-1 in dorsal root ganglion neurons occurs after nerve injury and results in an increased synaptic abundance of Cav2.2 channels in the spinal dorsal horn, thus enhancing the transmission of pain signals. Here, we report that large conductance calcium-activated potassium (BK) channels interact with the Cavα2δ subunit. Coexpression of BK channels with the Cav2 calcium channels reduces their cell-surface expression and whole-cell current density by competing the Cavα2δ subunit away from the Cav2 complex. Biochemical analysis reveals that the extracellular N terminus region of the BK channel is the key molecular determinant of this effect. Intrathecally delivered virus constructs encoding a membrane-anchored BK channel N terminus peptide produces long-lasting analgesia in mouse models of inflammatory and neuropathic pain. Collectively, our data reveal an endogenous ligand of the Cavα2δ subunit with analgesic properties.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.318
Threshold uncertainty score0.561

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.220
Teacher spread0.210 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations69
Published2018
Admission routes2
Has abstractyes

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