β <sub>2</sub> ‐Adrenoceptor regulation of the K <sup>+</sup> channel iK <sub>Ca</sub> 1 in human mast cells
Bibliographic record
Abstract
Human mast cells express the intermediate conductance Ca2+-activated K+ channel iKCa1, which opens following IgE-dependent activation. This results in cell membrane hyperpolarization and potentiation of both Ca2+ influx and degranulation. Mast cell activation is attenuated following exposure to beta2-adrenoceptor agonists such as salbutamol, an effect postulated to operate via intracellular cyclic AMP. In this study, we show that salbutamol closes iKCa1 in mast cells derived from human lung and peripheral blood. Salbutamol (1-10 microM) inhibited iKCa1 currents following activation with both anti-IgE and the iKCa1 opener 1-EBIO, and was reversed by removing salbutamol or by the addition of the selective beta2-adrenoceptor antagonist and inverse agonist ICI 118551. Interestingly, ICI 118551 consistently opened iKCa1 in quiescent cells, suggesting that constitutive beta2-receptor signaling suppresses channel activity. Manipulation of intracellular cAMP, Galphai, and Galphas demonstrates that the beta2-adrenergic effects are consistent with a membrane-delimited mechanism involving Galphas. This is the first demonstration that gating of the iKCa1 channel is regulated by a G protein-coupled receptor and provides a clearly defined mechanism for the mast cell "stabilizing" effect of beta2-agonists. Furthermore, the degree of constitutive beta2-receptor "tone" may control the threshold for human mast cell activation through the regulation of iKCa1.
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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 | 0.000 |
| 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 | 0.000 |
| 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".