Myosin-based regulation of twitch and tetanic contractions in mammalian skeletal muscle
- King's College London, United Kingdom
Abstract
Time-resolved X-ray diffraction from isolated fast-twitch muscles of the mouse was used to show how structural changes in the myosin-containing thick filaments contribute to the regulation of muscle contraction, extending the previous focus on regulation by the actin-containing thin filaments. This study shows that muscle activation involves the following sequence of structural changes: thin filament activation, disruption of the helical array of myosin motors characteristic of resting muscle, release of myosin motor domains from the folded conformation on the filament backbone, and actin attachment. Physiological force generation in the 'twitch' response of skeletal muscle to single action potential stimulation is limited by incomplete activation of the thick filament and the rapid inactivation of both filaments. Muscle relaxation after repetitive stimulation is accompanied by complete recovery of the folded motor conformation on the filament backbone but incomplete reformation of the helical array, revealing a structural basis for post-tetanic potentiation in isolated muscle.
Data availability
All source data for data analysed in this study are provided for figures 1 to 6.
Article and author information
Author details
Elisabetta Brunello
Funding
Medical Research Council (MR/R01700X/1)
- Cameron Hill
- Malcolm Irving
Diamond Light Source (SM21316-1)
- Cameron Hill
- Elisabetta Brunello
- Luca Fusi
- Jesús G Ovejero
- Malcolm Irving
British Heart Foundation Intermediate Basic Science Research Fellowship (FS/17/3/32604)
- Elisabetta Brunello
- Jesús G Ovejero
Sir Henry Dale Fellowship, Wellcome Trust and The Royal Society (210464/Z/18/Z)
- Luca Fusi
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 animals were housed and maintained following the ARRIVE guidelines (Kilkenny et al., 2010; PLOS Biology, 8:e1000412). Animals were sacrificed via cervical dislocation in compliance with the UK Home Office Animals (Scientific Procedures) Act 1986, Schedule 1.
Copyright
© 2021, Hill 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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Myosin-based regulation of twitch and tetanic contractions in mammalian skeletal muscle
eLife 10:e68211.
https://doi.org/10.7554/eLife.68211
