Ca <sub>v</sub> 3.1 Channels Modulate Ca <sub>v</sub> 1.2 Functional Coupling: Implications to Myogenic Response
Bibliographic record
Abstract
Introduction and Aim: Myogenic response is an autoregulatory arterial constriction to elevated blood pressure – a reflex essential for proper blood flow distribution. Historically, it’s mechanistic basis is explained as arterial depolarization opening voltage-gated Ca 2+ channels (VGCC), the primary subtype being L-type (Ca V 1.2). While unarguably important, additional regulatory mechanisms may exist including one where T-type (Ca V 3.1) Ca 2+ channels alone or in interaction with Ca V 1.2 play a facilitatory role in myogenic tone development. Methods: A detailed electrical analysis was completed using patch-clamp electrophysiology (whole-cell & cell-attached) on rodent cerebral arterial smooth muscle cells. Intracellular [Ca 2+ ] ([Ca 2+ ] i ) in resistant arteries was assessed using pressure myography and Fura-2AM. Results: Whole-cell patch-clamp revealed that pressure-like stimuli increased the Ca V 1.2, but not the Ca V 3.1 current. Single channel analysis tied the Ca V 1.2 activity rise to enhanced 1) functional coupling and 2) subunit trafficking to caveolae. Pressure-induced functional coupling was observed in intact arteries as manifested by elevated [Ca 2+ ] i (at 80 vs 20 mmHg) in the presence of 30 mM K + to standardize membrane potential (-40mV). To test the role of Ca V 3.1 in pressure-regulation of Ca V 1.2, single channel analysis was repeated in arterial myocytes from Ca V 3.1 −/− animals. Intriguingly, while pressure continued to foster Ca V 1.2 trafficking, it didn’t augment functional coupling. Likewise, we didn’t observe the elevated Ca 2+ response in arteries (at 80 vs 20 mmHg) when membrane potential was standardized. There was, however, evidence of higher baseline Ca V 1.2 activity in both experimental sets. Conclusions: Our results indicate that pressure increases Ca V 1.2 activity by enhancing perimembrane trafficking and functional coupling. We propose that the latter is tied to Ca V 3.1 and the induction of Ca 2+ -induced inactivation, an effect that partly dissipates as an artery depolarizes. The abolishment of Ca V 3.1 activity and thus the fine tuning of Ca V 1.2 functional coupling might facilitate arterial tone development in the hypertensive state. Supported by CIHR and Roraback Chair in Vascular Biology and Neuroscience. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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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) | 0.002 | 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".