Does G‐protein Coupled Receptor Activation Enhance Cerebral Arterial Mechanosensitivity
Bibliographic record
Abstract
This study determined whether the mechano‐sensitivity of a TRPC current in cerebral arterial smooth muscle could be enhanced by G‐protein coupled receptors (GPCRs) in a manner that facilitates myogenic tone development. An initial RT‐PCR analysis revealed the expression of TRPC1, 3, 6 & 7 mRNA in smooth muscle cells isolated from anterior cerebral arteries. Whole cell patch clamp electrophysiology subsequently confirmed the presence of a doubly rectifying current that displayed properties characteristic of a heteromultimeric TRPC3/6/7 channel. In particular, this non‐selective cation current was blocked by micromolar trivalents (Gd 3+ and Ln 3+ ) but insensitive to Cl − inhibitors (DIDS, niflumic acid, tamoxifen and flufenamic acid) and amiloride. GPCR agonists (UTP and U46619) augmented the activity of the TRPC‐like current as did a mechano‐stimulus like hyposmotic challenge (300 to 200 mOsm). While GPCR agonists can directly modulate TRPC‐like currents, this study found no evidence to suggest that they facilitate mechano‐sensitivity. The preceding findings were consistent with functional work which revealed that while GPCR agonists cause constriction, they do not enhance the myogenic reactivity of cerebral arteries. In closing, our findings suggest, in contrast to previous HEK expression studies, that GCPR activation does not enhance the mechano‐sensitivity of TRPC‐like currents nor the myogenic sensitivity of intact cerebral arteries. Supported by NSERC.
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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".