Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch

Autores
Vargas, Lorena Alejandra; Diaz, Romina Gisel; Swenson, Erik R.; Perez, Nestor Gustavo; Alvarez, Bernardo
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Myocardial stretch is an established signal that leads to hypertrophy. Myocardial stretch induces a first immediate force increase followed by a slow force response (SFR), which is a consequence of an increased Ca2+ transient that follows the NHE1 Na+/H+ exchanger activation. Carbonic anhydrase II (CAII) binds to the extreme COOH terminus of NHE1 and regulates its transport activity. We aimed to test the role of CAII bound to NHE1 in the SFR. The SFR and changes in intracellular pH (pHi) were evaluated in rat papillary muscle bathed with CO2/HCO3− buffer and stretched from 92% to 98% of the muscle maximal force development length for 10 min in the presence of the CA inhibitor 6-ethoxzolamide (ETZ, 100 μM). SFR control was 120 ± 3% (n = 8) of the rapid initial phase and was fully blocked by ETZ (99 ± 4%, n = 6). The SFR corresponded to a maximal increase in pHi of 0.18 ± 0.02 pH units (n = 4), and pHi changes were blocked by ETZ (0.04 ± 0.04, n = 6), as monitored by epifluorescence. NHE1/CAII physical association was examined in the SFR by coimmunoprecipitation, using muscle lysates. CAII immunoprecipitated with an anti-NHE1 antibody and the CAII immunoprecipitated protein levels increased 58 ± 9% (n = 6) upon stretch of muscles, assessed by immunoblots. The p90RSK kinase inhibitor SL0101–1 (10 μM) blocked the SFR of heart muscles after stretch 102 ± 2% (n = 4) and reduced the binding of CAII to NHE1, suggesting that the stretch-induced phosphorylation of NHE1 increases its binding to CAII. CAII/NHE1 interaction constitutes a component of the SFR to heart muscle stretch, which potentiates NHE1-mediated H+ transport in the myocardium.
Fil: Vargas, Lorena Alejandra. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Diaz, Romina Gisel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Swenson, Erik R.. University of Washington; Estados Unidos
Fil: Perez, Nestor Gustavo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Alvarez, Bernardo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Materia
Stretch
Carbonic Anhydrase Ii
Slow Force Response
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/11951
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/11951
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretchVargas, Lorena AlejandraDiaz, Romina GiselSwenson, Erik R.Perez, Nestor GustavoAlvarez, BernardoStretchCarbonic Anhydrase IiSlow Force Responsehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Myocardial stretch is an established signal that leads to hypertrophy. Myocardial stretch induces a first immediate force increase followed by a slow force response (SFR), which is a consequence of an increased Ca2+ transient that follows the NHE1 Na+/H+ exchanger activation. Carbonic anhydrase II (CAII) binds to the extreme COOH terminus of NHE1 and regulates its transport activity. We aimed to test the role of CAII bound to NHE1 in the SFR. The SFR and changes in intracellular pH (pHi) were evaluated in rat papillary muscle bathed with CO2/HCO3− buffer and stretched from 92% to 98% of the muscle maximal force development length for 10 min in the presence of the CA inhibitor 6-ethoxzolamide (ETZ, 100 μM). SFR control was 120 ± 3% (n = 8) of the rapid initial phase and was fully blocked by ETZ (99 ± 4%, n = 6). The SFR corresponded to a maximal increase in pHi of 0.18 ± 0.02 pH units (n = 4), and pHi changes were blocked by ETZ (0.04 ± 0.04, n = 6), as monitored by epifluorescence. NHE1/CAII physical association was examined in the SFR by coimmunoprecipitation, using muscle lysates. CAII immunoprecipitated with an anti-NHE1 antibody and the CAII immunoprecipitated protein levels increased 58 ± 9% (n = 6) upon stretch of muscles, assessed by immunoblots. The p90RSK kinase inhibitor SL0101–1 (10 μM) blocked the SFR of heart muscles after stretch 102 ± 2% (n = 4) and reduced the binding of CAII to NHE1, suggesting that the stretch-induced phosphorylation of NHE1 increases its binding to CAII. CAII/NHE1 interaction constitutes a component of the SFR to heart muscle stretch, which potentiates NHE1-mediated H+ transport in the myocardium.Fil: Vargas, Lorena Alejandra. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Diaz, Romina Gisel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Swenson, Erik R.. University of Washington; Estados UnidosFil: Perez, Nestor Gustavo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Alvarez, Bernardo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaAmerican Physiological Society2013-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/11951Vargas, Lorena Alejandra; Diaz, Romina Gisel; Swenson, Erik R.; Perez, Nestor Gustavo; Alvarez, Bernardo; Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch; American Physiological Society; American Journal Of Physiology-heart And Circulatory Physiology; 305; 2; 7-2013; 228-2370363-61351522-1539enginfo:eu-repo/semantics/altIdentifier/doi/10.1152/ajpheart.00055.2013info:eu-repo/semantics/altIdentifier/url/http://ajpheart.physiology.org/content/305/2/H228info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:10:43Zoai:ri.conicet.gov.ar:11336/11951instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:10:44.275CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch
title Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch
spellingShingle Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch
Vargas, Lorena Alejandra
Stretch
Carbonic Anhydrase Ii
Slow Force Response
title_short Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch
title_full Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch
title_fullStr Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch
title_full_unstemmed Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch
title_sort Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch
dc.creator.none.fl_str_mv Vargas, Lorena Alejandra
Diaz, Romina Gisel
Swenson, Erik R.
Perez, Nestor Gustavo
Alvarez, Bernardo
author Vargas, Lorena Alejandra
author_facet Vargas, Lorena Alejandra
Diaz, Romina Gisel
Swenson, Erik R.
Perez, Nestor Gustavo
Alvarez, Bernardo
author_role author
author2 Diaz, Romina Gisel
Swenson, Erik R.
Perez, Nestor Gustavo
Alvarez, Bernardo
author2_role author
author
author
author
dc.subject.none.fl_str_mv Stretch
Carbonic Anhydrase Ii
Slow Force Response
topic Stretch
Carbonic Anhydrase Ii
Slow Force Response
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Myocardial stretch is an established signal that leads to hypertrophy. Myocardial stretch induces a first immediate force increase followed by a slow force response (SFR), which is a consequence of an increased Ca2+ transient that follows the NHE1 Na+/H+ exchanger activation. Carbonic anhydrase II (CAII) binds to the extreme COOH terminus of NHE1 and regulates its transport activity. We aimed to test the role of CAII bound to NHE1 in the SFR. The SFR and changes in intracellular pH (pHi) were evaluated in rat papillary muscle bathed with CO2/HCO3− buffer and stretched from 92% to 98% of the muscle maximal force development length for 10 min in the presence of the CA inhibitor 6-ethoxzolamide (ETZ, 100 μM). SFR control was 120 ± 3% (n = 8) of the rapid initial phase and was fully blocked by ETZ (99 ± 4%, n = 6). The SFR corresponded to a maximal increase in pHi of 0.18 ± 0.02 pH units (n = 4), and pHi changes were blocked by ETZ (0.04 ± 0.04, n = 6), as monitored by epifluorescence. NHE1/CAII physical association was examined in the SFR by coimmunoprecipitation, using muscle lysates. CAII immunoprecipitated with an anti-NHE1 antibody and the CAII immunoprecipitated protein levels increased 58 ± 9% (n = 6) upon stretch of muscles, assessed by immunoblots. The p90RSK kinase inhibitor SL0101–1 (10 μM) blocked the SFR of heart muscles after stretch 102 ± 2% (n = 4) and reduced the binding of CAII to NHE1, suggesting that the stretch-induced phosphorylation of NHE1 increases its binding to CAII. CAII/NHE1 interaction constitutes a component of the SFR to heart muscle stretch, which potentiates NHE1-mediated H+ transport in the myocardium.
Fil: Vargas, Lorena Alejandra. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Diaz, Romina Gisel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Swenson, Erik R.. University of Washington; Estados Unidos
Fil: Perez, Nestor Gustavo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Alvarez, Bernardo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
description Myocardial stretch is an established signal that leads to hypertrophy. Myocardial stretch induces a first immediate force increase followed by a slow force response (SFR), which is a consequence of an increased Ca2+ transient that follows the NHE1 Na+/H+ exchanger activation. Carbonic anhydrase II (CAII) binds to the extreme COOH terminus of NHE1 and regulates its transport activity. We aimed to test the role of CAII bound to NHE1 in the SFR. The SFR and changes in intracellular pH (pHi) were evaluated in rat papillary muscle bathed with CO2/HCO3− buffer and stretched from 92% to 98% of the muscle maximal force development length for 10 min in the presence of the CA inhibitor 6-ethoxzolamide (ETZ, 100 μM). SFR control was 120 ± 3% (n = 8) of the rapid initial phase and was fully blocked by ETZ (99 ± 4%, n = 6). The SFR corresponded to a maximal increase in pHi of 0.18 ± 0.02 pH units (n = 4), and pHi changes were blocked by ETZ (0.04 ± 0.04, n = 6), as monitored by epifluorescence. NHE1/CAII physical association was examined in the SFR by coimmunoprecipitation, using muscle lysates. CAII immunoprecipitated with an anti-NHE1 antibody and the CAII immunoprecipitated protein levels increased 58 ± 9% (n = 6) upon stretch of muscles, assessed by immunoblots. The p90RSK kinase inhibitor SL0101–1 (10 μM) blocked the SFR of heart muscles after stretch 102 ± 2% (n = 4) and reduced the binding of CAII to NHE1, suggesting that the stretch-induced phosphorylation of NHE1 increases its binding to CAII. CAII/NHE1 interaction constitutes a component of the SFR to heart muscle stretch, which potentiates NHE1-mediated H+ transport in the myocardium.
publishDate 2013
dc.date.none.fl_str_mv 2013-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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://hdl.handle.net/11336/11951
Vargas, Lorena Alejandra; Diaz, Romina Gisel; Swenson, Erik R.; Perez, Nestor Gustavo; Alvarez, Bernardo; Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch; American Physiological Society; American Journal Of Physiology-heart And Circulatory Physiology; 305; 2; 7-2013; 228-237
0363-6135
1522-1539
url http://hdl.handle.net/11336/11951
identifier_str_mv Vargas, Lorena Alejandra; Diaz, Romina Gisel; Swenson, Erik R.; Perez, Nestor Gustavo; Alvarez, Bernardo; Inhibition of carbonic anhydrase prevents the Na /H exchanger 1-dependent slow force response to rat myocardial stretch; American Physiological Society; American Journal Of Physiology-heart And Circulatory Physiology; 305; 2; 7-2013; 228-237
0363-6135
1522-1539
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpheart.00055.2013
info:eu-repo/semantics/altIdentifier/url/http://ajpheart.physiology.org/content/305/2/H228
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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