Angiotensin II mobilizes intracellular calcium and activates pannexin‐1 channels in rat carotid body type II cells via AT<sub>1</sub>receptors
Bibliographic record
Abstract
Key points A locally generating, angiotensin II (ANG II) system is present in the rat carotid body (CB) and up‐regulation of this system occurs in certain pathophysiological situations, enhancing sympathetic activity. Here, we show that, similar to chemoreceptor type I cells, glial‐like type II cells also express functional AT1Rs, stimulation of which causes release of Ca2+from intracellular stores. ANG II–AT1R signalling in type II cells activates an inward current carried by pannexin‐1 (Panx‐1) channels which are known to act as conduits for release of ATP, a key CB excitatory neurotransmitter. Combined effects of ANG II and ATP, which also activates Panx‐1 currents via P2Y2 receptors, were synergistic; chelating intracellular Ca2+with BAPTA prevented Panx‐1 current activation. We propose that the excitatory function of ANG II in the CB involves dual actions at both type I and type II cells. Abstract A local angiotensin‐generating system is present in the carotid body (CB) and increased angiotensin II (ANG II) signalling contributes to enhanced CB excitation in chronic heart failure (CHF) and after chronic or intermittent hypoxia. ANG II actions have thus far been attributed solely to stimulation of AT1receptors (AT1Rs) on chemoreceptor type I cells. Here, we show that in dissociated rat CB cultures, ANG II also stimulates glial‐like type II cells, identified by P2Y2‐receptor‐induced intracellular Ca2+elevation (Δ[Ca2+]i). ANG II induced a dose‐dependent (EC50∼8 nm), robust Δ[Ca2+]iin type II cells that was reversibly abolished by the AT1R blocker losartan (1 μm). The ANG II‐induced Δ[Ca2+]ipersisted in Ca2+‐free medium but was sensitive to store depletion with cyclopiazonic acid (1 μm). Similar to P2Y2 receptor agonists, ANG II (20–1000 nm) activated pannexin‐1 (Panx‐1) current that was reversibly abolished by carbenoxolone (5 μm). This current arose with a variable delay and was reversibly inhibited by losartan. Repeated application of ANG II often led to current run‐down, attributable to AT1R desensitization. When applied to the same cell the combined actions of ANG II and ATP on Panx‐1 current were synergistic. Current induced by either ligand was inhibited by BAPTA‐AM (1 μm), suggesting that intracellular Ca2+signalling contributed to Panx‐1 channel activation. Because open Panx‐1 channels release ATP, a key CB excitatory neurotransmitter, it is plausible that paracrine stimulation of type II cells by ANG II contributes to enhanced CB excitability, especially in pathophysiological conditions such as CHF and sleep apnoea.
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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 | 0.001 |
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".