Involvement of TRPM4 in Stretch‐Induced Modulation of Lymphatic Pumping
Bibliographic record
Abstract
Rhythmic and phasic contractions of collecting lymphatic vessels are critically involved in tissue fluid homeostasis and immune response. This contractile activity, or lymphatic pumping, is exquisitely regulated by luminal fluid pressure. However, the molecular contributors of stretch‐induced lymphatic pumping are not known. Some members of the TRP channel family, in particular TRPM4,have been shown to respond to stretch or pressure and to contribute to myogenic vasoconstriction and vascular response to stretch. Using pressure myography, electrophysiology, pharmacology and quantitative real‐time PCR, we tested the hypothesis that TRPM4 is also a major contributor of the lymphatic vessel response to stretch. We demonstrated the expression of TRPM4 mRNA in rat mesenteric lymphatic vessels and showed that the contraction frequency of the vessels pressurized at 3 mmHg was inhibited in a concentration‐dependent manner by the TRPM4 blocker 9‐phenanthrol (IC 50 =1.2 µM). The blocker (10 µM) also inhibited the pressure‐induce increase in contraction frequency in an endothelium‐independent manner and caused a hyperpolarization of the lymphatic muscle. These findings suggest an important role for TRPM4 in the ability of lymphatic vessels to adapt their contractile activity to changes in intraluminal lymph pressure.
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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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".