ICC pacing mechanisms in intact mouse intestine differ from those in cultured or dissected intestine
Bibliographic record
Abstract
Pacing of mouse intestine is driven by spontaneous activity of a network of interstitial cells of Cajal in the myenteric plexus (ICC-MP). So far, highly dissected circular muscle (CM) strips from control and mutant mice lacking ICC-MP and isolated, cultured ICC from newborn control mice were used to analyze its properties. Using intact circular and longitudinal segments of intestine, we recently reported that there were both significant similarities and differences between pacing studied in segments and from isolated, dissected tissues. Here, we report additional similarities and differences in our model from those in highly reduced systems. Similar to cultured or dissected intestine, blockade of sarcoplasmic-endoplasmic reticulum Ca(2+) pumps with thapsigargin or cyclopiazonic acid reduced pacing frequency, but thapsigargin was less effective than in isolated, cultured ICC. Moreover, inhibition of inositol 1,4,5-trisphosphate (IP(3)) receptors with xestospongin C, a putative inhibitor of IP(3) receptors, failed to affect pacing but successfully blocked increased pacing frequency by phorbol ester. 2-Aminoethoxy-diphenylborate, a putative blocker of IP(3)-mediated calcium release, caused a significant decrease in the amplitude and frequency of contractions. The mitochondrial uncoupler carbonyl cyanide p-trifluormethoxyphenylhydrazone blocked pacing and KCl-induced contractions at a concentration of 1 microM. The cyclic nucleotide agonists sodium nitroprusside (SNP), forskolin, and 8-bromo-cGMP inhibited pacing in CM. In longitudinal muscle (LM), SNP and forskolin had little effect on pacing. Furthermore, dibutyryl-cAMP did not affect pacing in CM or LM. These results suggest that pacing in intact intestine is under partly similar regulatory control as in more reduced systems. However, pacing in intact intestine is not affected by xestospongin C, which abolishes pacing in isolated, cultured ICC and exhibits attenuated responses to thapsigargin. Also, major differences between LM and CM suggest a separate pacemaker may drive LM.
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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 | 0.001 |
| 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".