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Role of the JP45-Calsequestrin Complex on Calcium Entry in Slow Twitch Skeletal Muscles

Barbara Mosca1, Jan Eckhardt2, Leda Bergamelli1

  • 1Department of Life Science and Biotechnology, University of Ferrara, Via Borsari 46, 44100, Ferrara, Italy.

The Journal of Biological Chemistry
|May 19, 2016
PubMed

Insights

The JP45-CASQ complex negatively regulates excitation-coupled calcium entry (ECCE) in slow twitch muscles. Ablating both JP45 and calsequestrins (CASQs) enhances ECCE, supporting tetanic force.

Area of Science:

  • Muscle physiology
  • Calcium signaling
  • Sarcoplasmic reticulum function

Background:

  • Excitation-coupled calcium entry (ECCE) is crucial for muscle contraction.
  • Calsequestrins (CASQs) and JP45 are sarcoplasmic reticulum proteins involved in calcium handling.
  • The precise roles of JP45-CASQ interactions in ECCE and muscle force are not fully understood.

Purpose of the Study:

  • To investigate the roles of JP45 and calsequestrins (CASQ1 and CASQ2) in regulating calcium entry in slow twitch muscles.
  • To elucidate the functional consequences of JP45-CASQ interactions on excitation-coupled calcium entry (ECCE) and tetanic force development.

Main Methods:

  • Utilized various genetically modified mouse models, including triple knockout mice lacking JP45, CASQ1, and CASQ2.
  • Isolated flexor digitorum brevis (FDB) fibers and soleus muscles for physiological assessments.
  • Measured calcium transients and tetanic force development under different experimental conditions.

Main Results:

  • Ablation of both JP45 and CASQs (CASQ1 and CASQ2) significantly enhanced ECCE in FDB fibers.
  • Enhanced ECCE in triple KO mice relied on calcium entry through La(3+)- and nifedipine-sensitive channels.
  • The dynamic interaction between JP45 and CASQs, regulated by calcium concentrations, was identified as a key factor in ECCE modulation.
  • Ablation of JP45-CASQ complexes supported tetanic force development in slow twitch soleus muscles.

Conclusions:

  • The JP45-CASQ complex acts as a negative regulator of ECCE in slow twitch muscles.
  • Dynamic dissociation of JP45 from CASQs upon calcium release is essential for ECCE.
  • Tetanic force generation in slow twitch muscles is supported by the regulated interaction between JP45 and CASQs.
Keywords:
calcium-binding proteinexcitation-contraction coupling (E-C coupling)gene knockoutmuscle physiologysarcoplasmic reticulum (SR)

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