Role of bicarbonate in the regulation of intracellular pH in the mammalian ventricular myocyte
Bibliographic record
Abstract
Bicarbonate is important for pHi control in cardiac cells. It is a major part of the intracellular buffer apparatus, it is a substrate for sarcolemmal acid-equivalent transporters that regulate intracellular pH, and it contributes to the pHo sensitivity of steady-state pHi, a phenomenon that may form part of a whole-body response to acid/base disturbances. Both bicarbonate and H+/OH- transporters participate in the sarcolemmal regulation of pHi, namely Na(+)-HCO3-cotransport (NBC), Cl(-)-HCO3- exchange (i.e., anion exchange, AE), Na(+)-H+ exchange (NHE), and Cl(-)-OH- exchange (CHE). These transporters are coupled functionally through changes of pHi, while pHi is linked to [Ca2+]i through secondary changes in [Na+] mediated by NBC and NHE. Via such coupling, decreases of pHo and pHi can ultimately lead to an elevation of [Ca2+]i, thereby influencing cardiac contractility and electrical rhythm. Bicarbonate is also an essential component of an intracellular carbonic buffer shuttle that diffusively couples cytoplasmic pH to the sarcolemma and minimises the formation of intracellular pH microdomains. The importance of bicarbonate is closely linked to the activity of the enzyme carbonic anhydrase (CA). Without CA activity, intracellular bicarbonate-dependent buffering, membrane bicarbonate transport, and the carbonic shuttle are severely compromised. There is a functional partnership between CA and HCO3- transport. Based on our observations on intracellular acid mobility, we propose that one physiological role for CA is to act as a pH-coupling protein, linking bulk pH to the allosteric H+ control sites on sarcolemmal acid/base transporters.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".