Reduced Extracellular [Ca <sup>2+</sup> ] Increases the Sensitivity of Mouse EDL and Soleus to the K <sup>+</sup> ‐Induced Force Depression: Implication for the Increased Sensitivity of Hyperkalemic Periodic Paralysis Muscles to Calcium Levels
Bibliographic record
Abstract
Hyperkalemic periodic paralysis (HyperKPP) is a disease of altered skeletal muscle excitability due to missense mutations in the skeletal muscle Na + channel (Na V 1.4). It is primarily characterized by myotonic discharges between and during periods of paralysis that mainly affect limb muscles. The paralysis is induced by large membrane depolarizations associated with the increase in Na + influx and accumulation of extracellular [K + ] during the myogenic discharge. Patients can be alleviated of their paralysis by taking salbutamol and/or ingesting Ca 2+ . While salbutamol mechanism of action involves an improved resting membrane potential and an increase in Ca 2+ release, the effect of Ca 2+ is not well understood except that a large increase in extracellular [Ca 2+ ] e ([Ca 2+ ] e ) reduces the K + ‐induced force depression. The objective of this study was therefore to test the hypothesis that a reduced [Ca 2+ ] e increases the extent of the K + ‐induced force depression and reduces the salbutamol‐induced increase in force at elevated [K + ] e . A decrease in [Ca 2+ ] e from 2.4 mM to 0.3 mM had no effect on the tetanic force of both wild type mouse EDL and soleus when [K + ] e was at the normal 4.7 mM. However, it significantly shifted the tetanic force‐[K + ] e relationship to lower [K + ] e . At 2.4 mM Ca 2+ and 4.7 mM K + , HyperKPP EDL and soleus generated as much tetanic force as their wild type counterpart. However, decreases in [Ca 2+ ] e to 1.3 and 0.3 mM significantly reduced tetanic force at 4.7 mM and caused large and significant shift of the tetanic force‐[K + ] e relationship to lower [K + ] e . Lowering [Ca 2+ ] e did not affect the efficacy of salbutamol to increase tetanic force when it had been depressed by an increase in [K + ] e in either wild type or HyperKPP muscles. Considering that at 4.7 mM K + , several HyperKPP EDL and soleus fibers are depolarized and that the effect of lower [Ca 2+ ] e occurred when the cell membrane is depolarized by increases in [K + ] e , it is suggested that the increased sensitivity of HyperKPP muscles to Ca 2+ is primarily because of a large number of fibers with depolarized cell membrane even when [K + ] e is at its normal value of 4.7 mM. Support or Funding Information This study was supported by the Canadian Institute of Health Research (CIHR) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".