The molecular basis for the actions of K<sub>V</sub>β1.2 on the opening and closing of the K<sub>V</sub>1.2 delayed rectifier channel
Bibliographic record
Abstract
Cytosolic K(V)beta1 subunits co-assemble with transmembrane K(V)1 channel alpha-subunits and have complex effects on channel function. Fast inactivation, the most obvious effect conferred, is due to fast open channel block resulting from the binding of the N-terminus within the inner mouth of the pore. K(V)beta1 subunits also slow current deactivation, enhance slow inactivation and shift channel activation to more negative voltages, but the mechanisms underlying these actions are not known. Here we use voltage clamp fluorimetry at sites near the extracellular end of the S4 helix, the channel's primary voltage sensor, in combination with voltage clamp electrophysiology, to independently track the movement of the S4 helix along with ionic current, and thus identify the structural and mechanistic means by which the K(V)beta1.2 subunit confers its actions on the K(V)1.2 channel. We show that the negative shift in current activation is not due to direct actions of K(V)beta1.2 on the S4 segment. Instead, this shift results from an apparent saturation of channel activation at depolarized potentials as the extent of open channel block by the K(V)beta1.2 N-terminus progressively increases. The return of fluorescence to baseline is slowed along with current deactivation. According to our data, this is due to an inability of the activation gate to close while the K(V)beta1.2 N-terminus occupies the pore and strong coupling of the gate with the S4 segment. Together with data from previous studies, our findings provide a complete and coherent picture of the functional and structural interactions between K(V)beta1.2 and K(V)1.2.
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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 | 0.000 |
| 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 | 0.001 |
| 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".