Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice

Autores
Hashimoto, Katsuji; Pérez, Néstor Gustavo; Kusuoka, Hideo; Baker, Debra L.; Periasamy, Muthu; Marbán, Eduardo
Año de publicación
2000
Idioma
español castellano
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective: This study was undertaken to investigate the mechanism of altered contractility in hearts from transgenic mice overexpressing the sarcoplasmic reticulum (SR) Ca²⁺ ATPase (SERCA2a). In particular, we sought to determine whether the reported increase in contractility is freqnency-dependent, as might be expected if attributable to changes in SR Ca²⁺ loading. Methods: Intracellular [Ca²⁺] and contractile force were measured at room temperature (22 °C) simultaneously in fura-2-loaded isometrically-contracting trabeculae dissected from the hearts of FVB/N control (n=6) or SERCA2a transgenic (n=6) mice. Results: SERCA transgenics exhibit a positive force-frequency relationship, but this was flat in age- and strain-matched controls. SERCA transgenics exhibit a sizable increase in calcium transient amplitude relative to controls, with a concomitant increase in force generation at higher frequencies of stimulation. Amplitudes of Ca²⁺ transients (transgenics: 1.56 ± 0.09 μmol/l, controls: 1.21 ± 0.14) and twitches (transgenics: 21.71 ± 0.91 mN/mm², controls: 13.74 ± 1.67) were significantly different at 2.0 Hz stimulation (P < 0.05). Conclusion: An increase in SERCA expression increases the ability of the sarcoplasmic reticulum to store calcium, such that more calcium is available to be released during each heartbeat at higher stimulation rates.
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares
Materia
Medicina
Calcium
Ca-pump
contractile function
e-c coupling
SR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/133702
Acceder
id SEDICI_5232318fde3dc41ee8ccf715a8504565
oai_identifier_str oai:sedici.unlp.edu.ar:10915/133702
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic miceHashimoto, KatsujiPérez, Néstor GustavoKusuoka, HideoBaker, Debra L.Periasamy, MuthuMarbán, EduardoMedicinaCalciumCa-pumpcontractile functione-c couplingSRObjective: This study was undertaken to investigate the mechanism of altered contractility in hearts from transgenic mice overexpressing the sarcoplasmic reticulum (SR) Ca²⁺ ATPase (SERCA2a). In particular, we sought to determine whether the reported increase in contractility is freqnency-dependent, as might be expected if attributable to changes in SR Ca²⁺ loading. Methods: Intracellular [Ca²⁺] and contractile force were measured at room temperature (22 °C) simultaneously in fura-2-loaded isometrically-contracting trabeculae dissected from the hearts of FVB/N control (n=6) or SERCA2a transgenic (n=6) mice. Results: SERCA transgenics exhibit a positive force-frequency relationship, but this was flat in age- and strain-matched controls. SERCA transgenics exhibit a sizable increase in calcium transient amplitude relative to controls, with a concomitant increase in force generation at higher frequencies of stimulation. Amplitudes of Ca²⁺ transients (transgenics: 1.56 ± 0.09 μmol/l, controls: 1.21 ± 0.14) and twitches (transgenics: 21.71 ± 0.91 mN/mm², controls: 13.74 ± 1.67) were significantly different at 2.0 Hz stimulation (P < 0.05). Conclusion: An increase in SERCA expression increases the ability of the sarcoplasmic reticulum to store calcium, such that more calcium is available to be released during each heartbeat at higher stimulation rates.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculares2000-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf144-151http://sedici.unlp.edu.ar/handle/10915/133702spainfo:eu-repo/semantics/altIdentifier/issn/0300-8428info:eu-repo/semantics/altIdentifier/issn/1435-1803info:eu-repo/semantics/altIdentifier/doi/10.1007/s003950050176info:eu-repo/semantics/altIdentifier/pmid/10826507info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-29T15:36:59Zoai:sedici.unlp.edu.ar:10915/133702Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-29 15:36:59.396SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice
title Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice
spellingShingle Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice
Hashimoto, Katsuji
Medicina
Calcium
Ca-pump
contractile function
e-c coupling
SR
title_short Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice
title_full Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice
title_fullStr Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice
title_full_unstemmed Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice
title_sort Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice
dc.creator.none.fl_str_mv Hashimoto, Katsuji
Pérez, Néstor Gustavo
Kusuoka, Hideo
Baker, Debra L.
Periasamy, Muthu
Marbán, Eduardo
author Hashimoto, Katsuji
author_facet Hashimoto, Katsuji
Pérez, Néstor Gustavo
Kusuoka, Hideo
Baker, Debra L.
Periasamy, Muthu
Marbán, Eduardo
author_role author
author2 Pérez, Néstor Gustavo
Kusuoka, Hideo
Baker, Debra L.
Periasamy, Muthu
Marbán, Eduardo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Medicina
Calcium
Ca-pump
contractile function
e-c coupling
SR
topic Medicina
Calcium
Ca-pump
contractile function
e-c coupling
SR
dc.description.none.fl_txt_mv Objective: This study was undertaken to investigate the mechanism of altered contractility in hearts from transgenic mice overexpressing the sarcoplasmic reticulum (SR) Ca²⁺ ATPase (SERCA2a). In particular, we sought to determine whether the reported increase in contractility is freqnency-dependent, as might be expected if attributable to changes in SR Ca²⁺ loading. Methods: Intracellular [Ca²⁺] and contractile force were measured at room temperature (22 °C) simultaneously in fura-2-loaded isometrically-contracting trabeculae dissected from the hearts of FVB/N control (n=6) or SERCA2a transgenic (n=6) mice. Results: SERCA transgenics exhibit a positive force-frequency relationship, but this was flat in age- and strain-matched controls. SERCA transgenics exhibit a sizable increase in calcium transient amplitude relative to controls, with a concomitant increase in force generation at higher frequencies of stimulation. Amplitudes of Ca²⁺ transients (transgenics: 1.56 ± 0.09 μmol/l, controls: 1.21 ± 0.14) and twitches (transgenics: 21.71 ± 0.91 mN/mm², controls: 13.74 ± 1.67) were significantly different at 2.0 Hz stimulation (P < 0.05). Conclusion: An increase in SERCA expression increases the ability of the sarcoplasmic reticulum to store calcium, such that more calcium is available to be released during each heartbeat at higher stimulation rates.
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares
description Objective: This study was undertaken to investigate the mechanism of altered contractility in hearts from transgenic mice overexpressing the sarcoplasmic reticulum (SR) Ca²⁺ ATPase (SERCA2a). In particular, we sought to determine whether the reported increase in contractility is freqnency-dependent, as might be expected if attributable to changes in SR Ca²⁺ loading. Methods: Intracellular [Ca²⁺] and contractile force were measured at room temperature (22 °C) simultaneously in fura-2-loaded isometrically-contracting trabeculae dissected from the hearts of FVB/N control (n=6) or SERCA2a transgenic (n=6) mice. Results: SERCA transgenics exhibit a positive force-frequency relationship, but this was flat in age- and strain-matched controls. SERCA transgenics exhibit a sizable increase in calcium transient amplitude relative to controls, with a concomitant increase in force generation at higher frequencies of stimulation. Amplitudes of Ca²⁺ transients (transgenics: 1.56 ± 0.09 μmol/l, controls: 1.21 ± 0.14) and twitches (transgenics: 21.71 ± 0.91 mN/mm², controls: 13.74 ± 1.67) were significantly different at 2.0 Hz stimulation (P < 0.05). Conclusion: An increase in SERCA expression increases the ability of the sarcoplasmic reticulum to store calcium, such that more calcium is available to be released during each heartbeat at higher stimulation rates.
publishDate 2000
dc.date.none.fl_str_mv 2000-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/133702
url http://sedici.unlp.edu.ar/handle/10915/133702
dc.language.none.fl_str_mv spa
language spa
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/0300-8428
info:eu-repo/semantics/altIdentifier/issn/1435-1803
info:eu-repo/semantics/altIdentifier/doi/10.1007/s003950050176
info:eu-repo/semantics/altIdentifier/pmid/10826507
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
144-151
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
_version_ 1847428475723448320
score 13.10058

Publicaciones similares