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January 15, 2024Open Access

Loss of calpain 3 dysregulates store-operated calcium entry and its exercise response in mice

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Key result

Loss of Calpain 3 in mice resulted in elevated resting store-operated calcium entry and increased resting cytosolic Ca2+, but impaired exercise-induced SOCE activation and force production.

Population

Capn3 deficient (C3KO) and wildtype (WT) mice

Comparison

Single bout of treadmill running vs Wildtype (WT) mice and resting state

Design

Preclinical

Follow-up

1 hour post-exercise

Authors

KVKatelyn R. VillaniUniversity of FloridaRZRenjia ZhongUniversity of FloridaCHC. Spencer Henley‐BeasleyUniversity of Florida

Discussion

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Implication

Calpain 3 loss impairs exercise-induced SOCE in mice; leaves open its therapeutic targeting in human LGMD2A.

Structured PICO

P
Population
Capn3 deficient (C3KO) and wildtype (WT) mice were studied to evaluate the role of Calpain 3 in store-operated calcium entry and exercise response.
E
Exposure
Single bout of treadmill running
C
Comparator
Wildtype (WT) mice and resting state
O
Outcome
Store-Operated Calcium Entry (SOCE) activity and resting cytosolic Ca2+ levelssurrogate

Calpain 3 regulates store-operated calcium entry in skeletal muscle, and its loss impairs exercise-induced calcium homeostasis, contributing to LGMD2A pathology.

Limitations

  • Total ablation of Capn3 may not accurately replicate patient pathology where mutations are widely dispersed throughout the CAPN3 gene.

Cite This Study

Villani et al. (2024) studied Limb-Girdle Muscular Dystrophy 2A (LGMD2A). Capn3 deficiency vs. Wildtype (WT) mice was evaluated on Store-Operated Calcium Entry (SOCE) activity and exercise-induced force production. Loss of Calpain 3 in mice resulted in elevated resting store-operated calcium entry and increased resting cytosolic Ca2+, but impaired exercise-induced SOCE activation and force production.

synapsesocial.com/papers/6ab4d2ad2707a85be48d896ehttps://doi.org/10.1101/2024.01.12.575391
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Natural history of LGMD 2A for delineating outcome measures in clinical trials2016 · 81 citations
  2. 2Physical and Functional Cross Talk Between Endo-Sarcoplasmic Reticulum and Mitochondria in Skeletal Muscle2019 · 37 citations
  3. 3Constitutive assembly of Ca2+ entry units in soleus muscle from calsequestrin knockout mice2022 · 13 citations
  4. 4Novel role of calpain-3 in the triad-associated protein complex regulating calcium release in skeletal muscle2008 · 104 citations
  5. 5Exercise-dependent formation of new junctions that promote STIM1-Orai1 assembly in skeletal muscle2017 · 86 citations