Endothelial Inwardly Rectifying K <sup>+</sup> Channel Subunit 2.1 Critically Enables Flow‐mediated Dilation in Cerebral Resistance Arteries
Bibliographic record
Abstract
Cerebral blood flow is a highly regulated process tied to the expression of ion channels in endothelial and smooth muscle cells. Of particular note are endothelial inwardly rectifying K + channels (K IR ), membrane proteins that presumably sense hemodynamic stimuli such as blood flow. This study sought to clearly define the role of endothelial K IR 2.1 in cerebral arterial blood flow sensing using floxed control and endothelial K IR 2.1 ‐/‐ mice. Experiments progressed from single cell (patch‐clamp electrophysiology of cerebral endothelial and smooth muscle), to isolated vessel (myography of cerebral resistance arteries) and finally to intact organism (arterial spin‐labeling magnetic resonance imaging). Electrophysiological analysis confirmed the presence of K IR activity in endothelial cells from floxed but not endothelial K IR 2.1 ‐/‐ mice; the former was subsequently shown to be flow sensitive. Smooth muscle K IR activity was comparable among the two animal groups. Vessel experiments next revealed that flow‐induced vasodilation was diminished in endothelial K IR 2.1 ‐/‐ mice. In the absence of endothelium, Ba 2+ ‐induced constriction was comparable among the two groups consistent with preserved smooth muscle K IR activity. Intriguingly, the diminishment of cellular and tissue level responses in endothelial K IR 2.1 ‐/‐ mice did not lead to apparent cerebral flow abnormalities (cortex, cerebral nuclei, hippocampus, thalamus, hypothalamus and midbrain), at baseline or following a systemic blood pressure challenge (intraperitoneal phenylephrine). These findings underscore a role for endothelial K IR 2.1 activity in hemodynamic sensing, one that is subtle and dynamically balanced with other mechanisms that set cerebral arterial blood flow.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".