LRRC8A-containing chloride channel is crucial for cell volume recovery and survival under hypertonic conditions
Bibliographic record
Abstract
Significance Rapid regulatory volume increase (RVI) is important for cell survival under hypertonic conditions. RVI is driven by Cl − uptake via the Na–K–Cl cotransporter (NKCC), which is activated by WNK kinases following a reduction in intracellular [Cl − ]. However, how intracellular [Cl − ] is regulated to modulate the WNK–NKCC axis and engage a protective RVI remains unknown. Our work reveals that LRRC8A-containing chloride channel is a key protective factor against hypertonic shocks. Considering that LRRC8A (SWELL1) is typically activated by low ionic strength under hypotonic stress, our results posed another interesting question: what activates this chloride channel under hypertonic stress? We demonstrated that, upon hyperosmotic activation, the p38-MSK1 pathway gates LRRC8A-containing chloride channel to facilitate activation of WNK–NKCC and an effective RVI.
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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 | 0.000 | 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) | 0.000 | 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".