Integrin‐dependent and ‐independent potentiation of L‐type Calcium Current (Cav1.2) by cell stretch
Bibliographic record
Abstract
Recent studies in our lab using both native and heterologously expressed calcium channels (Cav1.2) indicate that L‐type calcium current is potentiated by activation of a5b1 integrin and requires PKA‐ and Src‐ phosphorylation of Cav1.2 C‐terminal residues. To test whether Cav1.2 channels are mechanosensitive and the possible role of integrins in this process, patch clamp methods were used to investigate the properties of Cav1.2 expressed in HEK 293 cells during intracellular application of positive pressure or more physiological, longitudinal two‐pipette stretch of a flexible membrane onto which cells were plated. The membrane was coated with either fibronectin or poly‐lysine to assess integrin‐dependent or ‐independent responses, respectively. In cells expressing the smooth muscle calcium channel isoform (Cav1.2b) alone or in combination with b2a/a2d‐1 accessory subunits, positive pipette pressures of 10~30 mmHg resulted in 20~45% increases in peak inward current. Similar results were found for the neuronal L‐type channel isoform Cav1.2c. Longitudinal stretch between 110 to 130% of resting cell length induced 25 to 60% graded increases in Cav1.2c current. The magnitude of the increase was significantly greater on fibronectin‐coated substrate than on poly‐lysine coated substrate. Preliminary findings showed that native L‐type calcium currents from VSMC exhibit similar mechanical sensitivity. Our results suggest that the Cav1.2 channel subunit shows a limited amount of intrinsic mechanosensitivity and that enhanced channel activity in response to longitudinal stretch may 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) | 0.002 | 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".