Pressure Regulation of Vascular L-type Calcium Channels
Bibliographic record
Abstract
Myogenic tone is dependent upon the activation of L-type Ca2+ channels and the rise in cytosolic [Ca2+]i. While L-type Ca2+ channel activation is often singularly linked to arterial depolarization, sparse evidence suggests that pressure itself may also enhance functional activity, through cooperative gating and trafficking. In this context, this study explored whether intravascular pressure indeed tune the myogenic response by enhancing the L-type Ca2+ channel trafficking and amplifying cooperative gating.Experimentation began in isolated smooth muscle cells (whole cell/single-channel patch clamp; immunohistochemistry; proximity ligation assay) and extended to intact arteries (pressure myography and Ca2+ measurements). Whole-cell electrophysiology revealed the ability of pressure stimuli to increase the L-type Ca2+ current, a response dependent on the intact cytoskeleton and enzymes tied to functional coupling (PKCα, AKAP150, PKA). Cell-attached electrophysiology confirmed whole-cell observations, registering increased coupling among L-type Ca2+ channels when cells were pressurized. Ensuing experiments on isolated arteries subsequently revealed linkage between intravascular pressure and enhanced L-type Ca2+ channel activity, independent of membrane depolarization.In closing, our results suggest there is more to L-type Ca2+ channel regulation than voltage gating and that pressure itself can enhance functional activity. Work continues to precisely define the pressure-sensitive signaling complexes within vascular smooth muscle. Supported by the Canadian Institute for Health Research, National Institute of Health and the Rorabeck Chair in Vascular Biology and Neuroscience. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".