Co‐release of ATP and ACh mediates hypoxic signalling at rat carotid body chemoreceptors
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Bibliographic record
Abstract
Using functional co-cultures of rat carotid body (CB) O2 chemoreceptors and 'juxtaposed' petrosal neurones (JPNs), we tested whether ATP and ACh acted as co-transmitters. Perforated-patch recordings from JPNs often revealed spontaneous and hypoxia-evoked (PO2 approximately 5 mmHg) excitatory postsynaptic responses. The P2X purinoceptor blocker, suramin (50 microM) or a nicotinic ACh receptor (nAChR) blocker (hexamethonium, 100 microM; mecamylamine, 1 microM) only partially inhibited these responses, but together, blocked almost all activity. Under voltage clamp (-60 mV), fast perfusion of 100 microM ATP over hypoxia-responsive JPNs induced suramin-sensitive (IC50 = 73 microM), slowly-desensitizing, inward currents (IATP) with time constant of activation tauon = 30.6 +/- 4. 8 ms (n = 7). IATP reversed at 0.33 +/- 3.7 mV (n = 4), and the dose-response curve was fitted by the Hill equation (EC50 = 2.7 microM; Hill coefficient approximately 0.9). These purinoceptors contained immunoreactive P2X2 subunits, but their activation by alpha,beta-methylene ATP (alpha,beta-meATP; EC50 = 2.1 microM) suggests they are P2X2/P2X3 heteromultimers. Suramin and nAChR blockers inhibited the extracellular chemosensory discharge in the intact rat carotid body-sinus nerve preparation in vitro. Further, P2X2 immunoreactivity was widespread in rat petrosal ganglia in situ, and co-localized in neurones expressing the CB chemo-afferent marker, tyrosine hydroxylase (TH). P2X2 labelling in the CB co-localized with nerve-terminal markers, and was intimately associated with TH-positive type 1 cells. Thus ATP and ACh are co-transmitters during chemotransduction in the rat carotid body.
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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 | 0.000 | 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
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Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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