Inhibition of store‐operated Ca<sup>2+</sup> influx by acidic extracellular pH in cultured human microglia
Bibliographic record
Abstract
The effects of extracellular acidification on Ca(2+)-dependent signaling pathways in human microglia were investigated using Ca(2+)-sensitive fluorescence microscopy. Adenosine triphosphate (ATP) was used to elicit Ca(2+) responses primarily dependent on the depletion of intracellular endoplasmic reticulum (ER) stores, while platelet-activating factor (PAF) was used to elicit responses primarily dependent on store-operated channel (SOC) influx of Ca(2+). The duration of transient responses induced by ATP was not significantly different in standard physiological pH 7.4 (mean duration 30.2 +/- 2.5 s) or acidified pH 6.2 (mean duration 31.7 +/- 2.8 s) extracellular solutions. However, the time course of the PAF response at pH 7.4 was significantly reduced by 87% with external pH at 6.2. These results suggest that acidification of extracellular solutions inhibits SOC entry of Ca(2+) with little or no effect on depletion of ER stores. Changes of extracellular pH over the range from 8.6 to 6.2 during the development of a sustained SOC influx induced by PAF resulted in instantaneous modulation of SOC amplitude indicating a rapidly reversible effect of pH on this Ca(2+) pathway. Whole-cell patch clamp recordings showed external acidification blocked depolarization-activated outward K(+) current indicating cellular depolarization may be involved in the acid pH inhibition. Since SOC mediated influx of Ca(2+) is strongly modulated by membrane potential, the electrophysiological data suggest that acidification may act to inhibit SOC by cellular depolarization. These results suggest that acidification observed during cerebral ischemia may alter microglial responses and functions.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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)
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".