Differential Frequency Dependence of P2Y<sub>1</sub>- and P2Y<sub>2</sub>- Mediated Ca<sup>2</sup><sup>+</sup>Signaling in Astrocytes
Bibliographic record
Abstract
ATP is a key extracellular messenger that mediates the propagation of Ca 2+ waves in astrocyte networks in various regions of the CNS. ATP-mediated Ca 2+ signals play critical roles in astrocyte proliferation and differentiation and in modulating neuronal activity. The actions of ATP on astrocytes are via two distinct subtypes of P2Y purinoceptors, P2Y1 and P2Y2 receptors (P2Y1Rs and P2Y2Rs), G-protein coupled receptors that stimulate mobilization of intracellular Ca 2+ ([Ca 2+]i) via the phospholipase Cbeta-IP3 pathway. We report here that P2Y1R-mediated and P2Y2R-mediated Ca 2+ responses differentially show two forms of activity-dependent negative feedback. First, Ca 2+ responses mediated by either receptor exhibit slow depression that is independent of stimulation frequency. Second, responses mediated by P2Y1Rs, but not those mediated by P2Y2Rs, show rapid oscillations after high-frequency stimulation. We demonstrate that the oscillations are mediated by recruiting negative feedback by protein kinase C, and we map the site responsible for the effect of protein kinase C to Thr339 in the C terminus of P2Y1R. We propose that frequency-dependent changes in ATP-mediated Ca 2+ signaling pathways may modulate astrocyte function and astrocyte-neuron signaling in the CNS.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".