BK Potassium Channels Suppress Cavα2δ Subunit Function to Reduce Inflammatory and Neuropathic Pain
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".