Capillary Oxygen Triggers Conducted Hyperpolarization and Dilation Independent of Extracellular K <sup>+</sup> and Endothelial K <sub>IR</sub> 2.1
Bibliographic record
Abstract
The matching of red blood cell (RBC) supply to oxygen demand is an intricate process which requires generation of a capillary stimulus and triggering of a transduction process that dilates upstream arterioles. The sensor’s identity, the stimulus it generates and the mechanisms that enables it are openly debated and a source of active inquiry. This study tested whether extracellular K + is the stimulus and if capillary K IR 2.1 channels enable upstream arteriolar dilation via conduction. Experiments were performed in vivo, using a live microcirculatory preparation (extensor digitorum longus); the local oxygen environment was tightly controlled (custom stage insert) and capillary RBC kinetics monitored in mice lacking endothelial K IR 2.1 or connexin 40. Dropping PO 2 on the muscle surface (53 mmHg to 15 mmHg or 0 mmHg (3 min)) induced a stark microvascular response in control animals (RBC supply rate, velocity and hematocrit increased by 56%, 28% an 18%, respectively) without diminishing mitochondrial respiration. This blood flow response failed to materialize in connexin 40 −/− mice. As this response was absent, capillary RBC O 2 saturation was lower under normal conditions in the connexin 40 −/− animals. In contrast, endothelial K IR 2.1 −/− mice reacted normally to O 2 challenges, with RBC supply rate, velocity and hematocrit rising by 43%, 28%, and 11%, respectively. These findings show that coupling O 2 demand‐to‐O 2 supply requires coordinated electrical signaling among cells connected by gap junctions comprised of connexin 40. They also show that endothelial K IR 2.1 channels are not responsible for initiating the hyperpolarization needed to drive conduction. These findings begin the process of restructuring our understanding of blood flow regulation and how O 2 initiates this process independent of metabolite production. Support or Funding Information This work was funded by NSERC Discovery grants to CGE and to DGW.
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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".