Increased GABAA receptor open probability: Adaptive mechanisms to cope with anoxia in the painted turtle
Bibliographic record
Abstract
The western painted turtle is the most anoxia-tolerant tetrapod known, surviving ∼ 4 months at 3 °C without oxygen. In the mammalian brain, absence of oxygen leads to hyper-excitability and cell death within minutes. A major mechanism by which painted turtles survive anoxia is a large increase of γ-aminobutyric acid (GABA) in the brain leading to a dominating Cl - conductance that clamps membrane potential near the reversal potential of the GABA A receptor. Whole-cell GABA A receptor currents are known to increase with the onset of anoxia because of increased presynaptic GABA release, we hypothesized that GABA A receptor currents may also exhibit a large increase due to increased channel open time. To investigate this, we used cell-attached single-channel patch-clamp electrophysiological techniques to measure GABA A receptor open times (P open ) during a normoxic to anoxic transition in pyramidal neurons in turtle brain cortical sheets. GABA A receptor P open significantly increased 13-fold with the onset of anoxia and was blocked by the inclusion of the protein kinase C (PKC) activator PMA phorbol-12-myristate-13-acetate. Indicating the receptor was regulated by covalent modification. To investigate the molecular evolutionary mechanisms underlying these adaptations, we used codon-based likelihood models to detect changes in selective pressure amongst the GABA A receptor subunit genes. We found positive selection in GABRB2 and GABRB3 at sites near their ligand binding interface, likely impacting channel kinetics associated with hypoxia-tolerance. The elucidation of the adaptations associated with increased hypoxia tolerance furthers our understanding of physiological adaptations to extreme low-oxygen environments.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 source (direct Gemma or distilled Codex), 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".