Bicarbonate homeostasis in excitable tissues: role of AE3 Cl <sup>−</sup> /HCO <sub>3</sub> <sup>−</sup> exchanger and carbonic anhydrase XIV interaction
Bibliographic record
Abstract
Bicarbonate transport and metabolism are key elements of normal cellular function. Two alternate transcripts of anion exchanger 3 (AE3), full-length (AE3fl) and cardiac (AE3c), are expressed in central nervous system (CNS), where AE3 catalyzes electroneutral Cl(-)/HCO(3)(-) exchange across the plasma membrane of neuronal and glial cells of CNS. Anion exchanger isoforms, AE3fl and AE3c, associate with the carbonic anhydrases (CA) CAII and CAIV, forming a HCO(3)(-) transport metabolon, to maximize HCO(3)(-) flux across the plasma membrane. CAXIV, with catalytic domain anchored to the extracellular surface, is also expressed in CNS. Here physical association of AE3 and CAXIV was examined by coimmunoprecipitation experiments, using mouse brain and retinal lysates. CAXIV immunoprecipitated with anti-AE3 antibody, and both AE3 isoforms were immunoprecipitated using anti-CAXIV antibody, indicating CAXIV and AE3 interaction in the CNS. Confocal images revealed colocalization of CAXIV and AE3 in Müller and horizontal cells, in the mouse retina. Cl(-)/HCO(3)(-) exchange activity of AE3fl was investigated in transiently transfected human embryonic kidney 293 cells, using intracellular fluorescence measurements of BCECF, to monitor intracellular pH. CAXIV increased the rate of AE3fl-mediated HCO(3)(-) transport by up to 120%, which was suppressed by the CA inhibitor acetazolamide. Association of AE3 and CAXIV may represent a mechanism to enhance disposal of waste CO(2) and to balance pH in excitable tissues.
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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 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| 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 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".