Distinct myoprotective roles of cardiac sarcolemmal and mitochondrial K <sub>ATP</sub> channels during metabolic inhibition and recovery
Bibliographic record
Abstract
The protective roles of sarcolemmal (sarc) and mitochondrial (mito) KATP channels are unclear despite their apparent importance to ischemic preconditioning. We examined these roles by monitoring intracellular calcium ([Ca]int), using fura-2 and fluo-3, in enzymatically isolated rat right ventricular myocytes. Myocyte mortality, estimated using a trypan blue assay, changed approximately in parallel with changes in [Ca]int. Chemically induced hypoxia (CIH), induced by application of cyanide and 2-deoxy-glucose, caused a steady rise in [Ca]int. Calcium increased more rapidly on 'reoxygenation' by return to control solutions. The protein kinase C (PKC) activator PMA abolished both phases of calcium increase. The mitoKATP channel-selective blocker 5-hydroxydecanoate partially prevented the PMA-induced protection during CIH, but not during reoxygenation. In contrast, HMR 1098, a sarcKATP channel-selective blocker, abolished protection only during the reoxygenation. Adenosine (A1) receptor activation prevented or reduced increases in [Ca]int and improved cell viability via a PKC and mito/sarcKATP channel-dependent mechanism. PKC-dependent protection against cytoplasmic calcium increases was also observed in a human cell line (tsA201) transiently expressing sarcKATP channels. Protection was abolished only during the reoxygenation phase by the amino acid substitution (T180A) in the pore-forming Kir6.2 subunit, a mutation previously shown to prevent PKC-dependent modulation. Our data suggest that sarc and mitoKATP channel populations play distinct protective roles, triggered by PKC and/or adenosine, during chemically induced hypoxia/reoxygenation.
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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) | 0.001 | 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".