Diaphragm of Hyperkalemic Periodic Paralysis Mouse Has No Contractility Abnormality Compared to the Robust Abnormalities in EDL and Soleus
Bibliographic record
Abstract
Hyperkalemic periodic paralysis (HyperKPP) is an autosomal dominant disease that is caused by mutations in the SCN4A gene that encodes for the Nav1.4 channel, the skeletal muscle isoform of Na + channels. HyperpKPP patients suffer from both myotonia and limb paralysis. The myotonia is the result of large membrane depolarization due to large Na + influx through defective NaV1.4 channels, while the paralysis is caused by increases in extracellular [K + ] [[K + ]e). However; even though diaphragm also expresses Nav1.4 channels, HyperKPP patients rarely suffer from respiratory distress, as expected with any paralysis. Despite the fact that Na + influxes through mutated NaV1.4 channels in diaphragm, soleus and EDL muscles from a HyperKPP mouse model are all significantly greater than in their WT counterparts, the HyperKPP diaphragm is the only muscles being spared from the K + ‐induced paralysis. The lack of paralysis in diaphragm is not related to any significant increases in Na + K + ATPase α‐1 and α‐2 protein content, which actually only increased in HyperKPP EDL. Measurements of resting membrane potential (resting E m ) and force demonstrated that the lower force generation in HyperKPP EDL and soleus compared to wild type muscles at different [K + ] e was in part related to greater membrane depolarization when [K + ]e was increased. However, for a given [K + ]e or resting EM, HyperKPP diaphragm generated more force than WT diaphragm. It is proposed that another membrane component spares diaphragm from HyperKPP symptoms, possibly the Na + Ca 2+ exchanger which can increase [Ca 2+ ]i during contraction when [Na + ]i is elevated as it does in cardiac muscle.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.010 | 0.002 |
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".