Potentiation of L‐Type Calcium Current (Cav1.2) by Intracellular Positive Pressure: Role of the Cav1.2 C‐terminus
Bibliographic record
Abstract
The myogenic response is the rapid and maintained constriction of a blood vessel in response to pressure elevation. A role for integrins in this mechanotransduction process has been suggested. Recent studies in our lab indicate that L‐type calcium current is potentiated by activation of α5β1 integrin for both native and heterologously expressed channels, requiring PKA‐ and Src‐ phosphorylation of Cav1.2 C‐terminal residues. To test whether Cav1.2 channels are intrinsically mechanosensitive, patch clamp methods were used to investigate the properties of Cav1.2 expressed in HEK 293 cells during intracellular application of positive pressure to expand the plasma membrane. In cells expressing the pore‐forming smooth muscle isoform (Cav1.2b) alone or Cav1.2b plus β2a/α2δ‐1 accessory subunits, positive pipette pressures of 10~30 mmHg resulted in 20~45% increases in peak inward barium current, which was substantially less than the potentiation by α5β1 integrin activation (95%). Similar results were found for the neuronal L‐type channel isoform Cav1.2c (+/−β1b/α2δ). Neither intracellular application of PKA inhibitor peptide nor mutagenesis of the PKA phosphorylation site on Cav1.2 at Ser 1901 blocked the effect of positive pressure. Our results suggest that the Cav1.2 calcium channel subunit is intrinsically mechanosensitive and that enhanced channel activity in response to intracellular positive pressure may not involve the integrin‐extracellular matrix axis.
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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".