Ion transport deficits observed during colitis are associated with functional inhibition, but not decreased expression, of IK <sub>Ca</sub> channels ‐ possible involvement of PKC
Bibliographic record
Abstract
Adequate hydration of the intestinal epithelial surface is essential for gut function and is regulated by active ion transport. We have shown in a dextran sodium sulfate (DSS) model of colitis that colonic secretory responses to bethanechol are abolished and responses to histamine, thapsigargin, cyclopiazonic acid, and the calcium ionophore A23187 are severely attenuated. We hypothesized that this could be due to decreased expression and/or activity of intermediate‐conductance Ca 2+ ‐activated K + channels ( KCNN4 /IK Ca ). Analysis of mRNA extracted from colonic crypts showed no transcriptional differences in KCNN4 . Western blotting revealed no changes in IK Ca protein expression, although calmodulin was increased in crypts from DSS‐treated mice. Direct activation of IK Ca channels with DCEBIO produced a highly diminished ion transport response in DSS compared to controls. This apparent functional inhibition of IK Ca channels during DSS colitis could be due to aberrant Ca 2+ signaling, possibly via protein kinase C (PKC). Indeed, ion transport responses in control tissue are sensitive to non‐selective PKC inhibition; also, PKC activation with phorbol 12‐myristate 13‐acetate led to increased ion transport in control colonic tissue that was greatly reduced in DSS tissue. This hyposecretory phenotype may represent a strategy to counter the malabsorptive diarrhea associated with colitis. Funded by the CCFC.
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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) | 0.002 | 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".