Alzheimer’s amyloid peptides mediate hypoxic up‐regulation of L‐type Ca <sup>2+</sup> channels
Bibliographic record
Abstract
We examined the effects of chronic hypoxia on recombinant human L-type Ca2+ channel alpha1C subunits stably expressed in HEK 293 cells, using whole-cell patch-clamp recordings. Current density was dramatically increased following 24 h exposure to chronic hypoxia (CH), and membrane channel protein levels were enhanced. CH also increased the levels of Alzheimer's amyloid beta peptides (AbetaPs), determined immunocytochemically. Pharmacological prevention of AbetaP production (via exposure to inhibitors of secretase enzymes that are required to cleave AbetaP from its precursor protein) prevented hypoxic augmentation of currents, as did inhibition of vesicular trafficking with bafilomycin A1. The enhancing effect of AbetaPs or CH were abolished following incubation with the monoclonal 3D6 antibody, raised against the extracellular N' terminus of AbetaP. Immunolocalization and immunoprecipitation studies provided compelling evidence that AbetaPs physically associated with the alpha1C subunit, and this association was promoted by hypoxia. These data suggest an important role for AbetaPs in mediating the increase in Ca2+ channel activity following CH and show that AbetaPs act post-transcriptionally to promote alpha1C subunit insertion into (and/or retention within) the plasma membrane. Such an action will likely contribute to the Ca2+ dyshomeostasis of Alzheimer's disease and may contribute to the mechanisms underlying the known increased incidence of this neurodegenerative disease following hypoxic episodes.
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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 | 0.000 |
| 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) | 0.001 | 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".