A Correlation Between Dexmedetomidine-Induced Biphasic Increases in Free Cytosolic Calcium Concentration and Energy Metabolism in Astrocytes
Bibliographic record
Abstract
UNLABELLED: The alpha(2)-adrenergic agonist, dexmedetomidine, increases free cytosolic calcium concentration ([Ca(2+)](i)) in astrocytes, but not in neurons. The present study was performed to characterize the origin of the increased Ca(2+) in mouse astrocytes cultured from the cerebral cortex, the dose dependence of the effect, and its functional consequences. The increase in [Ca(2+)](i) was independent of extracellular Ca(2+), but was inhibited by dantrolene, showing that it is derived from intracellular stores; two peaks in [Ca(2+)](i) were demonstrated-one around 100 nM dexmedetomidine and the other in the low micromolar range. A similar dose dependence was found for pyruvate dehydrogenation, the initial metabolic reaction of oxidative degradation of pyruvate, suggesting that the these events are interrelated. The alpha(2)-adrenergic antagonist, yohimbine, abolished the metabolic stimulation at both peaks. However, whereas the increase in [Ca(2+)] (i) at 100 nM is abolished by yohimbine, increase in the micromolar range was partly inhibited by yohimbine and partly by idazoxan, an inhibitor at the imidazoline-preferring site. The stimulation of energy metabolism in cerebrocortical astrocytes may explain the repeated finding that dexmedetomidine does not decrease oxidative metabolism in the brain in vivo. The functional importance of the additional imidazoline receptor-mediated increase in [Ca(2+)](i) at large dexmedetomidine concentrations is unknown. IMPLICATIONS: Cytosolic calcium concentration and metabolism were measured in cultured astrocytes, the predominant glial cells. The results suggest that dexmedetomidine may owe its anesthetic effects to a Ca(2+)-dependent increase in astrocytic energy metabolism, allowing these cells to more effectively remove extracellular glutamate and potassium ions, and thus, decreasing neuronal excitability.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".