Distinct EC coupling mechanism drives spatial control of vascular tone in cerebral arteries
Bibliographic record
Abstract
Cerebral arterial networks consist of thousands of segments that work together and in isolation, tuning the magnitude and distribution of brain blood flow. The existence of spatially distinct responses suggests that distinct excitation‐contraction (EC) coupling mechanisms are encoded into each arterial segment. This study sought to define which EC coupling mechanisms enable cerebral arterial segments to work together and in isolation, from one another. Using both theoretical and experimental approaches, we show that multi‐segmental responses require the sharing of charge via gap junctions. This process of “electrical communication” enables arteries to equilibrate membrane potential, synchronize Ca 2+ concentration and coordinate myosin light chain phosphorylation among large populations of smooth muscle cells. In contrast, isolated vessel behavior was independent of charge sharing and electromechanical coupling. It depended upon: 1) the voltage‐independent generation of Ca 2+ waves; and 2) direct catalytic subunit inhibition of myosin light chain phosphatase. The latter was found to be driven by protein kinase C and the phosphorylation of CPI‐17. Subsequent work revealed that the presence of distinct EC coupling mechanisms enabled multi‐segmental and isolated responses to simultaneously but independently co‐exist in a single artery. As such, the magnitude and distribution of brain blood flow can be concurrently tuned depending on the nature of the originating stimulus. Translationally, these findings indicate that the ‘one‐size‐fits‐all” strategy to treating blood flow abnormalities should be reconsidered and tailored to the underlying dysfunction in EC coupling. Support or Funding Information This work is supported by an operating grant to Dr Welsh from the Natural Science and Engineering Council of Canada (NSERC). Dr Welsh is the Roraback Chair in Neuroscience and Vascular Biology at the University of Western Ontario. A. Zechariah is supported by Canadian Institutes of Health Research (CIHR) Postdoctoral scholarship, Alberta Innovates Postdoctoral scholarship and Eyes High Postdoctoral fellowship.
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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 | 0.000 |
| 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".