Myosin-based regulation of twitch and tetanic contractions in mammalian skeletal muscle

Time-resolved X-ray diffraction of isolated fast-twitch muscles of mice 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 s...

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Main Authors: Cameron Hill, Elisabetta Brunello, Luca Fusi, Jesús G Ovejero, Malcolm Irving
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-06-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/68211
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author Cameron Hill
Elisabetta Brunello
Luca Fusi
Jesús G Ovejero
Malcolm Irving
author_facet Cameron Hill
Elisabetta Brunello
Luca Fusi
Jesús G Ovejero
Malcolm Irving
author_sort Cameron Hill
collection DOAJ
description Time-resolved X-ray diffraction of isolated fast-twitch muscles of mice 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 a complete recovery of the folded motor conformation on the filament backbone but by incomplete reformation of the helical array, revealing a structural basis for post-tetanic potentiation in isolated muscles.
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spelling doaj.art-f41ef1eeccfb4eef9dd63e3d7248b90b2022-12-22T03:37:49ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.68211Myosin-based regulation of twitch and tetanic contractions in mammalian skeletal muscleCameron Hill0https://orcid.org/0000-0002-0815-5109Elisabetta Brunello1https://orcid.org/0000-0003-3167-4828Luca Fusi2https://orcid.org/0000-0003-3992-0114Jesús G Ovejero3https://orcid.org/0000-0003-3774-6589Malcolm Irving4https://orcid.org/0000-0001-6419-3583Randall Centre for Cell & Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London, London, United KingdomRandall Centre for Cell & Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London, London, United KingdomRandall Centre for Cell & Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London, London, United KingdomRandall Centre for Cell & Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London, London, United KingdomRandall Centre for Cell & Molecular Biophysics, New Hunt’s House, Guy’s Campus, King’s College London, London, United KingdomTime-resolved X-ray diffraction of isolated fast-twitch muscles of mice 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 a complete recovery of the folded motor conformation on the filament backbone but by incomplete reformation of the helical array, revealing a structural basis for post-tetanic potentiation in isolated muscles.https://elifesciences.org/articles/68211skeletal musclemuscle regulationmuscle contractionmyosinx-ray diffraction
spellingShingle Cameron Hill
Elisabetta Brunello
Luca Fusi
Jesús G Ovejero
Malcolm Irving
Myosin-based regulation of twitch and tetanic contractions in mammalian skeletal muscle
eLife
skeletal muscle
muscle regulation
muscle contraction
myosin
x-ray diffraction
title Myosin-based regulation of twitch and tetanic contractions in mammalian skeletal muscle
title_full Myosin-based regulation of twitch and tetanic contractions in mammalian skeletal muscle
title_fullStr Myosin-based regulation of twitch and tetanic contractions in mammalian skeletal muscle
title_full_unstemmed Myosin-based regulation of twitch and tetanic contractions in mammalian skeletal muscle
title_short Myosin-based regulation of twitch and tetanic contractions in mammalian skeletal muscle
title_sort myosin based regulation of twitch and tetanic contractions in mammalian skeletal muscle
topic skeletal muscle
muscle regulation
muscle contraction
myosin
x-ray diffraction
url https://elifesciences.org/articles/68211
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AT lucafusi myosinbasedregulationoftwitchandtetaniccontractionsinmammalianskeletalmuscle
AT jesusgovejero myosinbasedregulationoftwitchandtetaniccontractionsinmammalianskeletalmuscle
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