Regulation of Cl<sup>−</sup>−Hco<sub>3</sub><sup>−</sup> exchangers by cAMP‐dependent protein kinase in adult rat hippocampal CA1 neurons
Bibliographic record
Abstract
The contributions of HCO(3)(-)-dependent, DIDS-sensitive mechanisms to the maintenance of steady-state pH(i), and the regulation of their activities by cAMP-dependent protein kinase (PKA), were investigated in CA1 neurons with the H(+)-sensitive fluorophore, BCECF. The addition of HCO(3)(-)/CO(2) to neurons with "low" (pH(i) < or = 7.20) and "high" (pH(i) > 7.20) initial pH(i) values under Hepes-buffered conditions, increased and decreased steady-state pH(i), respectively. Conversely, under HCO(3)(-)/CO(2)-buffered conditions, DIDS caused pH(i) to decrease and increase in neurons with low and high initial pH(i) values, respectively. In the presence, but not the absence, of HCO(3)(-), the PKA inhibitor Rp-adenosine-3',5'-cyclic monophosphorothioate (Rp-cAMPS; 50 microM) evoked DIDS-sensitive increases and decreases in pH(i) in neurons with low and high initial pH(i) values, respectively. In contrast, in neurons with low initial pH(i) values, activation of PKA with the Sp isomer of cAMPS (Sp-cAMPS; 25 microM) elicited increases in pH(i) that were smaller in the presence than in the absence of HCO(3)(-), whereas in neurons with high initial pH(i) values, Sp-cAMPS-evoked rises in pH(i) were larger in the presence than in the absence of HCO(3)(-); the differences between the effects of Sp-cAMPS on pH(i) under the different buffering conditions were attenuated by DIDS. Consistent with the possibility that changes in the activities of HCO(3)(-)-dependent, DIDS-sensitive mechanisms contribute to the steady-state pH(i) changes evoked by the PKA modulators, in neurons with initial pH(i) values < or = 7.20, Rp-cAMPS concurrently inhibited Na(+)-independent Cl(-)-HCO(3)(-) exchange and stimulated Na(+)-dependent Cl(-)-HCO(3)(-) exchange; in contrast, Sp-cAMPS concurrently stimulated Na(+)-independent Cl(-)-HCO(3)(-) exchange and inhibited Na(+)-dependent Cl(-)-HCO(3)(-) exchange. Data from a limited number of neurons with initial pH(i) values > 7.20 suggested that the directions of the reciprocal changes in anion exchange activities (inhibition or stimulation) evoked by Rp- and Sp-cAMPS may be opposite in cells with low vs. high resting pH(i) values. Taken together, the results indicate that the effects of modulating PKA activity on steady-state pH(i) in rat CA1 neurons under HCO(3)(-)/CO(2)-buffered conditions reflect not only changes in Na(+)-H(+) exchange activity but also changes in Na(+)-dependent and Na(+)-independent Cl(-)-HCO(3)(-) exchange activity that, in turn, may be dependent upon the initial pH(i).
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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 | 0.000 | 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 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".