Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels
Bibliographic record
Abstract
ABSTRACT Many voltage-dependent ion channels are regulated by accessory proteins, although the underlying mechanisms and consequences are often poorly understood. We recently reported a novel function of the amino acid transporter Slc7a5 as a powerful regulator of Kv1.2 voltage-dependent activation. In this study, we report that Kv1.1 channels are also regulated by Slc7a5, albeit with different functional outcomes. In heterologous expression systems, Kv1.1 exhibits prominent current enhancement (‘disinhibition’) with holding potentials more negative than −120 mV. Disinhibition of Kv1.1 is strongly attenuated by shRNA knockdown of endogenous Slc7a5. We investigated a variety of chimeric combinations of Kv1.1 and Kv1.2, demonstrating that exchange of the voltage-sensing domain controls the sensitivity and response to Slc7a5. Overall, our study highlights additional Slc7a5-sensitive Kv1 subunits, and demonstrates that features of Slc7a5 sensitivity can be swapped by exchanging voltage-sensing domains. IMPACT STATEMENT The voltage-sensing mechanism of a subfamily of potassium channels can be powerfully modulated in unconventional ways, by poorly understood regulatory partners.
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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 | 0.000 |
| 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".