P2Y2 receptor activation opens pannexin‐1 channels in rat carotid body type II cells: potential role in amplifying the neurotransmitter ATP
Bibliographic record
Abstract
Key points Carotid body (CB) chemoreceptor complexes consist of receptor type I cells, intimately associated with glia‐like type II cells whose function is poorly understood. We show that type II cells in the rat CB express gap junction‐like proteins, pannexin‐1 (Panx‐1) channels, which form non‐selective pores permeable to ions and large molecules such as ATP, a key CB neurotransmitter. Activation of purinergic P2Y2 receptors on type II cells led to a rise in intracellular Ca 2+ , and a prolonged membrane depolarization due to opening of Panx‐1 channels. In a CB co‐culture model, where purinergic P2X2/3‐expressing petrosal neurones served as a reporter or biosensor of ATP release, we show that selective activation of P2Y2 receptors on type II cells can lead to ATP release via Panx‐1 channels. We propose that type II cells may function as amplifiers of the neurotransmitter ATP during chemotransduction, via the mechanism of ATP‐induced ATP release. Abstract Signal processing in the carotid body (CB) is initiated at receptor glomus (or type I) cells which depolarize and release the excitatory neurotransmitter ATP during chemoexcitation by hypoxia and acid hypercapnia. Glomus cell clusters (GCs) occur in intimate association with glia‐like type II cells which express purinergic P2Y2 receptors (P2Y2Rs) but their function is unclear. Here we immunolocalize the gap junction‐like protein channel pannexin‐1 (Panx‐1) in type II cells and show Panx‐1 mRNA expression in the rat CB. As expected, type II cell activation within or near isolated GCs by P2Y2R agonists, ATP and UTP (100 μ m ), induced a rise in intracellular [Ca 2+ ]. Moreover in perforated‐patch whole cell recordings from type II cells, these agonists caused a prolonged depolarization and a concentration‐dependent, delayed opening of non‐selective ion channels that was prevented by Panx‐1 blockers, carbenoxolone (5 μ m ) and 4,4′‐diisothiocyano‐2,2′‐stilbenedisulfonic acid (DIDS; 10 μ m ). Because Panx‐1 channels serve as conduits for ATP release, we hypothesized that paracrine, type II cell P2Y2R activation leads to ATP‐induced ATP release. In proof‐of‐principle experiments we used co‐cultured chemoafferent petrosal neurones (PNs), which express P2X2/3 purinoceptors, as sensitive biosensors of ATP released from type II cells. In several cases, UTP activation of type II cells within or near GCs led to depolarization or increased firing in nearby PNs, and the effect was reversibly abolished by the selective P2X2/3 receptor blocker, pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS; 10 μ m ). We propose that CB type II cells may function as ATP amplifiers during chemotransduction via paracrine activation of P2Y2Rs and Panx‐1 channels.
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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 | 0.000 |
| 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 | 0.001 |
| 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".