Orai1- and Orai2-, but not Orai3-mediated I <sub>CRAC</sub> is regulated by intracellular pH
Bibliographic record
Abstract
ABSTRACT Three Orai (Orai1, Orai2 and Orai3) and two STIM (STIM1 and STIM2; st romal interaction m olecule) mammalian protein homologues constitute major components of the store-operated Ca 2+ entry mechanism. When co-expressed with STIM1, Orai1, Orai2 and Orai3 form highly selective Ca 2+ channels with properties of Ca 2+ release activated Ca 2+ (CRAC) channels. Despite the high level of homology between Orai proteins, CRAC channels formed by different Orai isoforms have distinctive properties, particularly with regards to Ca 2+ dependent inactivation, inhibition/potentiation by 2-APB and sensitivity to reactive oxygen species. This study characterises and compares the regulation of Orai1, Orai2- and Orai3-mediated CRAC current (I CRAC ) by intracellular pH. Using whole-cell patch clamping of HEK293T cells heterologously expressing Orai and STIM1 we show that I CRAC formed by each Orai homologue has a unique sensitivity to changes in intracellular pH (pH i ). Orai1-mediated I CRAC exhibits a strong dependence on pH i of both current amplitude and the kinetics of Ca 2+ dependent inactivation. In contrast, Orai2 amplitude, but not kinetics, depends on pH i , whereas Orai3 shows no dependence on pH i at all. Investigation of different Orai1-Orai3 chimeras suggests that pH i dependence of Orai1 resides in both, the N-terminus and intracellular loop 2, and may also involve pH-dependent interactions with STIM1.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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".