Transverse tubule remodeling enhances Orai1-dependent Ca2+ entry in skeletal muscle
- University of Rochester School of Medicine and Dentistry, United States
- University G d' Annunzio of Chieti, Italy
Abstract
Exercise promotes the formation of intracellular junctions in skeletal muscle between stacks of sarcoplasmic reticulum (SR) cisternae and extensions of transverse-tubules (TT) that increase co-localization of proteins required for store-operated Ca2+ entry (SOCE). Here we report that SOCE, peak Ca2+ transient amplitude and muscle force production during repetitive stimulation are increased after exercise in parallel with the time course of TT association with SR-stacks. Unexpectedly, exercise also activated constitutive Ca2+ entry coincident with a modest decrease in total releasable Ca2+ store content. Importantly, this decrease in releasable Ca2+ store content observed after exercise was reversed by repetitive high-frequency stimulation, consistent with enhanced SOCE. The functional benefits of exercise on SOCE, constitutive Ca2+ entry and muscle force production were lost in mice with muscle-specific loss of Orai1 function. These results indicate that TT association with SR-stacks enhances Orai1-dependent SOCE to optimize Ca2+ dynamics and muscle contractile function during acute exercise.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Simona Boncompagni
Funding
National Institutes of Health (AR059646)
- Robert T Dirksen
- Feliciano Protasi
Italian Ministry of Education, University and Research (PRIN #2015ZZR4W3)
- Feliciano Protasi
Alfred and Eleanor Wedd Fund
- Antonio Michelucci
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal studies were designed to minimize animal suffering and were approved by the local University Committee on Animal Resources and Animal Ethical Committees at the University of Chieti and the University of Rochester, respectively.(UCAR-2006-114E).
Reviewing Editor
- Richard S Lewis, Stanford University School of Medicine, United States
Publication history
- Received: April 10, 2019
- Accepted: October 24, 2019
- Accepted Manuscript published: October 28, 2019 (version 1)
- Version of Record published: November 7, 2019 (version 2)
- Version of Record updated: November 18, 2019 (version 3)
Copyright
© 2019, Michelucci et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Transverse tubule remodeling enhances Orai1-dependent Ca2+ entry in skeletal muscle
eLife 8:e47576.
https://doi.org/10.7554/eLife.47576
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