Store-Operated Ca <sup>2+</sup> Channels Mediate Microdomain Ca <sup>2+</sup> Signals and Amplify Gq-Coupled Ca <sup>2+</sup> Elevations in Capillary Pericytes
Bibliographic record
Abstract
Abstract Pericytes are multifunctional cells of the vasculature that are vital to brain homeostasis, yet many of their fundamental physiological properties remain unexplored. Ca 2+ is a ubiquitous second messenger across cell-types, where it mediates diverse functions such as contractility and gene transcription. It is therefore important to understand the cellular mechanisms underlying Ca 2+ signalling in capillary pericytes. Here, we performed pharmacological and ion substitution experiments to investigate the mechanisms underlying pericyte Ca 2+ signaling in acute cortical brain slices of PDGFRβ-GCaMP6f mice. We report that in mid-capillary bed pericytes (≥ 4 th branch order), spontaneous microdomain Ca 2+ signals are dependent on extracellular Ca 2+ , but largely independent of depolarization, L- and T-type voltage-gated calcium channels (VGCCs), and TRPC3/6 channels. In contrast, these microdomain signals were inhibited by multiple Orai channel blockers, including the specific antagonist GSK-7975A. Furthermore, capillary pericytes exhibited classical store operated calcium entry (SOCE) following store depletion that was sensitive to GSK-7975A and required for amplification of intracellular Ca 2+ increases evoked by the vasoconstrictor endothelin-1. These results suggest that Orai SOCE mediates microdomain Ca 2+ signals at rest and amplifies Gq-GPCR coupled Ca 2+ elevations in capillary pericytes. Thus, SOCE is a major regulator of pericyte Ca 2+ and a target for manipulating their function in health and disease.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.003 | 0.003 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.002 | 0.004 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.003 | 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; both teacher heads agree on what is shown here.
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".