Energy Metabolism During Fatigue In Fdb Muscle Is Impaired By The Lack Of KAtp Channel Activity
Bibliographic record
Abstract
PURPOSE: In skeletal muscle, the KATP channel is crucial in preventing fiber damage during exercise and fatigue. The channel is activated when energy levels fall and thus behaves as an energy sensor. Once activated, it directly reduces action potential amplitude, which then lowers Ca2+ release and force production. It is believed that together the latter effects lower the activity of the Ca2+ATPase and myosin ATPase in order to prevent damaging ATP depletion. So far, it remains unknown how the KATP channel affects energy metabolism during fatigue in skeletal muscle. The objective of this study was thus to determine whether the absence of KATP channel activity results in lower ATP levels and an impaired capacity to generate ATP during fatigue. METHODS: FDB bundles were fatigued with 1 tetanic contraction/sec for 180s at 37°C. KATP channel deficient fibers were obtained using fibers from Kir6.2-/- mice, which are null mice for the Kir6.2 gene that encodes for the protein forming the channel pore. Muscles were freeze-clamped in liquid nitrogen at different times during fatigue for metabolite determination. PCr, ATP and lactate were determined using enzymatic tests. The amount of glucosyl units entering glycolysis was calculated from glycogen breakdown and glucose uptake (using the 3H-2DG marker). The amount of unaccounted glucosyl units (or the total amount of intermediate metabolites) was calculated by subtracting the amount of lactate and 14CO2 (produced from 14C6-glucose) from the amount entering glycolysis. RESULTS: During fatigue the decreases in PCr were not different between W.T. and Kir6.2-/- FDB. ATP levels significantly decreased during the first 40 s of fatigue to a greater extent in Kir6.2-/- than W.T. FDB. It then reincreased during the next two min in W.T. but not in Kir6.2-/- FDB. Glucose uptake was greater while glycogen breakdown was smaller in W.T. than in Kir6.2-/- FDB. However, the amount of glucosyl units entering glycolysis was the same between the two muscle groups. Surprisingly, the amount of lactate produced was significantly greater in W.T. than in Kir6.2-/- FDB and the difference could not be explained by a greater difference in 14CO2 production. Consequently, the amount of unaccounted glucosyl units was greater in Kir6.2-/- than in W.T. FDB. CONCLUSION: The lack of KATP channel activity during fatigue significantly impaired energy metabolism in which the capacity of producing ATP during fatigue is reduced in Kir6.2-/- than W.T. FDB. This impairment may also be one of the causes of fiber damage in KATP channel deficient muscles.
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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) | 0.002 | 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".