The conductance of KCNQ2 and its pathogenic variants is determined by individual subunit gating
Bibliographic record
Abstract
KCNQ2 channel subunits form part of the M-current and underlie one of the major potassium currents throughout the human nervous system, regulating resting membrane potentials, shaping action potentials, and impeding repetitive neuronal firing. However, how individual subunits within tetramers control channel functionality remains unresolved. Here, we investigate (i) whether opening of KCNQ2 channels requires a concerted step or can result from independent subunit activation and (ii) how individual subunits regulate gate opening and conductance. The E140R mutation in the S2 segment prevents activated voltage sensor conformations, but concatemeric constructs containing up to three E140R subunits retain KCNQ2-like currents. The underlying single-channel currents show subconductance levels resulting from limitations in inner gate dimensions, determined by the number of activated subunits and their spatial arrangement. Channel opening is allosteric and requires activation of only a single subunit, which can accentuate the influence of clinically relevant heterozygous mutations at threshold voltages.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".