Lipopolysaccharide reduces electrical coupling between microvascular endothelial cells of wild type but not connexin40 null mice in tyrosine‐, PKA‐ and ERK1/2‐dependent manner
Bibliographic record
Abstract
Electrical coupling along the endothelium is central in the arteriolar conducted response and in control of vascular resistance. It has been shown that exposure of endothelium to lipopolysaccharide (LPS, an initiating factor in sepsis) reduces intercellular communication in vitro and in vivo . The molecular basis for this reduction is not known. We examined the effect of LPS on electrical coupling in monolayers of cultured microvascular endothelial cells (MMEC) derived from the mouse hindlimb skeletal muscle. To assess coupling, we measured the spread of electrical current injected into the monolayer and computed the intercellular resistance (inverse measure of coupling). LPS (10 μg/ml, 1 h) reduced coupling (i.e., increased resistance) in MMEC isolated from wild type, Cx37 null mutant and Cx43 G60S nonfunctional mutant mice, but not in MMEC derived from Cx40 null mutant mice. LPS also activated JNK1/2 and ERK1/2 MAP kinases. Pretreatment of WT monolayers with ERK1/2 inhibitor U0126 (20 μM, 1 h) prevented the LPS‐induced decrease in coupling, while inhibition of JNK1/2 with SP600125 (20 μM, 1 h) had no effect. Furthermore, inhibition of tyrosine kinases with PP‐2 (10 nM, 1 h), and activation of PKA by 8‐bromo‐cAMP (1 mM, 5 min) also prevented the reduction in coupling. We propose that LPS reduces inter‐endothelial electrical coupling via tyrosine‐, PKA‐ and ERK1/2‐dependent signaling that targets Cx40. We suggest this mechanism contributes to compromised arteriolar function following LPS exposure. (Supported by CIHR and HSFO).
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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".