Hyposmotic Challenge Inhibits Inward Rectifying K <sup>+</sup> Channels in Cerebral Arterial Smooth Muscle Cells
Bibliographic record
Abstract
This study sought to define whether inward rectifying K + (K IR ) channels were modulated by vasoactive stimuli known to depolarize and constrict intact cerebral arteries. Using pressure myography and patch clamp electrophysiology, initial experiments revealed a Ba 2+ ‐sensitive K IR current in cerebral arterial smooth muscle cells that was active over a physiological range of membrane potentials and whose inhibition led to arterial depolarization and constriction. Subsequent real‐time PCR, western blot and immunohistochemical analyses established the expression of both K IR 2.1 and K IR 2.2 in cerebral arterial smooth muscle cells. Vasoconstrictor agonists known to depolarize and constrict rat cerebral arteries, including uridine triphosphate, U46619, and 5‐HT had no discernable effect on whole‐cell K IR activity. In contrast, a hyposmotic challenge that activates mechano‐sensitive ion channels, elicited a rapid and sustained inhibition of K IR . The hyposmotic induced‐inhibition of K IR was: mimicked by the PKC agonist, phorbol‐12‐myristate‐13‐acetate; and inhibited by Calphostin C, a PKC inhibitor. These findings suggest that by modulating PKC, mechanical stimuli can regulate K IR and consequently the electrical and mechanical state of intact cerebral arteries. We propose that the mechano‐regulation of K IR plays a role in the development of myogenic tone. Supported by CIHR, NIH, and AHFMR.
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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) | 0.001 | 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".