Cargando…
Cooling intact and demembranated trabeculae from rat heart releases myosin motors from their inhibited conformation
Myosin filament–based regulation supplements actin filament–based regulation to control the strength and speed of contraction in heart muscle. In diastole, myosin motors form a folded helical array that inhibits actin interaction; during contraction, they are released from that array. A similar stru...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823665/ https://www.ncbi.nlm.nih.gov/pubmed/35089319 http://dx.doi.org/10.1085/jgp.202113029 |
_version_ | 1784646850929754112 |
---|---|
author | Ovejero, Jesus G. Fusi, Luca Park-Holohan, So-Jin Ghisleni, Andrea Narayanan, Theyencheri Irving, Malcolm Brunello, Elisabetta |
author_facet | Ovejero, Jesus G. Fusi, Luca Park-Holohan, So-Jin Ghisleni, Andrea Narayanan, Theyencheri Irving, Malcolm Brunello, Elisabetta |
author_sort | Ovejero, Jesus G. |
collection | PubMed |
description | Myosin filament–based regulation supplements actin filament–based regulation to control the strength and speed of contraction in heart muscle. In diastole, myosin motors form a folded helical array that inhibits actin interaction; during contraction, they are released from that array. A similar structural transition has been observed in mammalian skeletal muscle, in which cooling below physiological temperature has been shown to reproduce some of the structural features of the activation of myosin filaments during active contraction. Here, we used small-angle x-ray diffraction to characterize the structural changes in the myosin filaments associated with cooling of resting and relaxed trabeculae from the right ventricle of rat hearts from 39°C to 7°C. In intact quiescent trabeculae, cooling disrupted the folded helical conformation of the myosin motors and induced extension of the filament backbone, as observed in the transition from diastole to peak systolic force at 27°C. Demembranation of trabeculae in relaxing conditions induced expansion of the filament lattice, but the structure of the myosin filaments was mostly preserved at 39°C. Cooling of relaxed demembranated trabeculae induced changes in motor conformation and filament structure similar to those observed in intact quiescent trabeculae. Osmotic compression of the filament lattice to restore its spacing to that of intact trabeculae at 39°C stabilized the helical folded state against disruption by cooling. The myosin filament structure and motor conformation of intact trabeculae at 39°C were largely preserved in demembranated trabeculae at 27°C or above in the presence of Dextran, allowing the physiological mechanisms of myosin filament–based regulation to be studied in those conditions. |
format | Online Article Text |
id | pubmed-8823665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-88236652022-02-23 Cooling intact and demembranated trabeculae from rat heart releases myosin motors from their inhibited conformation Ovejero, Jesus G. Fusi, Luca Park-Holohan, So-Jin Ghisleni, Andrea Narayanan, Theyencheri Irving, Malcolm Brunello, Elisabetta J Gen Physiol Article Myosin filament–based regulation supplements actin filament–based regulation to control the strength and speed of contraction in heart muscle. In diastole, myosin motors form a folded helical array that inhibits actin interaction; during contraction, they are released from that array. A similar structural transition has been observed in mammalian skeletal muscle, in which cooling below physiological temperature has been shown to reproduce some of the structural features of the activation of myosin filaments during active contraction. Here, we used small-angle x-ray diffraction to characterize the structural changes in the myosin filaments associated with cooling of resting and relaxed trabeculae from the right ventricle of rat hearts from 39°C to 7°C. In intact quiescent trabeculae, cooling disrupted the folded helical conformation of the myosin motors and induced extension of the filament backbone, as observed in the transition from diastole to peak systolic force at 27°C. Demembranation of trabeculae in relaxing conditions induced expansion of the filament lattice, but the structure of the myosin filaments was mostly preserved at 39°C. Cooling of relaxed demembranated trabeculae induced changes in motor conformation and filament structure similar to those observed in intact quiescent trabeculae. Osmotic compression of the filament lattice to restore its spacing to that of intact trabeculae at 39°C stabilized the helical folded state against disruption by cooling. The myosin filament structure and motor conformation of intact trabeculae at 39°C were largely preserved in demembranated trabeculae at 27°C or above in the presence of Dextran, allowing the physiological mechanisms of myosin filament–based regulation to be studied in those conditions. Rockefeller University Press 2022-01-28 /pmc/articles/PMC8823665/ /pubmed/35089319 http://dx.doi.org/10.1085/jgp.202113029 Text en © 2022 Ovejero et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ovejero, Jesus G. Fusi, Luca Park-Holohan, So-Jin Ghisleni, Andrea Narayanan, Theyencheri Irving, Malcolm Brunello, Elisabetta Cooling intact and demembranated trabeculae from rat heart releases myosin motors from their inhibited conformation |
title | Cooling intact and demembranated trabeculae from rat heart releases myosin motors from their inhibited conformation |
title_full | Cooling intact and demembranated trabeculae from rat heart releases myosin motors from their inhibited conformation |
title_fullStr | Cooling intact and demembranated trabeculae from rat heart releases myosin motors from their inhibited conformation |
title_full_unstemmed | Cooling intact and demembranated trabeculae from rat heart releases myosin motors from their inhibited conformation |
title_short | Cooling intact and demembranated trabeculae from rat heart releases myosin motors from their inhibited conformation |
title_sort | cooling intact and demembranated trabeculae from rat heart releases myosin motors from their inhibited conformation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823665/ https://www.ncbi.nlm.nih.gov/pubmed/35089319 http://dx.doi.org/10.1085/jgp.202113029 |
work_keys_str_mv | AT ovejerojesusg coolingintactanddemembranatedtrabeculaefromratheartreleasesmyosinmotorsfromtheirinhibitedconformation AT fusiluca coolingintactanddemembranatedtrabeculaefromratheartreleasesmyosinmotorsfromtheirinhibitedconformation AT parkholohansojin coolingintactanddemembranatedtrabeculaefromratheartreleasesmyosinmotorsfromtheirinhibitedconformation AT ghisleniandrea coolingintactanddemembranatedtrabeculaefromratheartreleasesmyosinmotorsfromtheirinhibitedconformation AT narayanantheyencheri coolingintactanddemembranatedtrabeculaefromratheartreleasesmyosinmotorsfromtheirinhibitedconformation AT irvingmalcolm coolingintactanddemembranatedtrabeculaefromratheartreleasesmyosinmotorsfromtheirinhibitedconformation AT brunelloelisabetta coolingintactanddemembranatedtrabeculaefromratheartreleasesmyosinmotorsfromtheirinhibitedconformation |