Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac Hypertrophy

Autores
Espejo, María Sofía; Orlowski, Alejandro; Sørensen, Trine M.; Matchkov, Vladimir V.; Aiello, Ernesto Alejandro; Boedtkjer, Ebbe
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Aim: Metabolic disturbances challenge pH homeostasis in cardiomyocytes. The electroneutral Na+,HCO3 --cotransporter NBCn1/Slc4a7 mediates net acid extrusion, and genetic variation in SLC4A7 contributes to human hypertension and cardiovascular risk. Nonetheless, the cardiac consequences of disrupted NBCn1 expression and function remain unclear. Here, we test the hypothesis that NBCn1, either directly or indirectly, influences cardiac structure, contractile function, and electrophysiological properties.Methods: Based on mice with global loss of NBCn1, we measure intracellular pH in atria and ventricles of the heart (fluorescence microscopy), membrane potential responses (patch clamping), electro- and echocardiographic variables, blood pressure (telemetry), and cardiac dimensions (in vivo and postmortem analyses).Results: We find that protein and mRNA expression of NBCn1 are more prominent in atrial than in ventricular cardiomyocytes. Disruption of NBCn1 expression lowers Na+,HCO3 --cotransport activity more than 50% in atria without significantly influencing net acid extrusion activity of ventricular cardiomyocytes. Loss of NBCn1 is associated with hypertension (blood pressure increased by ~15 mmHg), cardiac hypertrophy (heart/body weight increased by ~10%), and prolonged ventricular isovolumic relaxation time (increased by ~25%). NBCn1 knockout does not affect cardiomyocyte size, collagen content in the heart wall, overall cardiac contractile function, electrophysiological properties of ventricular cardiomyocytes, or the electrocardiogram.Conclusion: NBCn1 is a main mechanism of Na+,HCO3 --cotransport in atrial tissue and contributes substantially to net acid extrusion during intracellular acidification. NBCn1 does not play any major direct role in ventricular cardiomyocytes of unchallenged mice, but global knockout of NBCn1 increases systemic blood pressure and results in the development of cardiac hypertrophy.
Fil: Espejo, María Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Orlowski, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Sørensen, Trine M.. University Aarhus; Dinamarca
Fil: Matchkov, Vladimir V.. University Aarhus; Dinamarca
Fil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Boedtkjer, Ebbe. University Aarhus; Dinamarca
Materia
Heart
Atria
Hypertrophy
NBCn1
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/282356
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/282356
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac HypertrophyEspejo, María SofíaOrlowski, AlejandroSørensen, Trine M.Matchkov, Vladimir V.Aiello, Ernesto AlejandroBoedtkjer, EbbeHeartAtriaHypertrophyNBCn1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Aim: Metabolic disturbances challenge pH homeostasis in cardiomyocytes. The electroneutral Na+,HCO3 --cotransporter NBCn1/Slc4a7 mediates net acid extrusion, and genetic variation in SLC4A7 contributes to human hypertension and cardiovascular risk. Nonetheless, the cardiac consequences of disrupted NBCn1 expression and function remain unclear. Here, we test the hypothesis that NBCn1, either directly or indirectly, influences cardiac structure, contractile function, and electrophysiological properties.Methods: Based on mice with global loss of NBCn1, we measure intracellular pH in atria and ventricles of the heart (fluorescence microscopy), membrane potential responses (patch clamping), electro- and echocardiographic variables, blood pressure (telemetry), and cardiac dimensions (in vivo and postmortem analyses).Results: We find that protein and mRNA expression of NBCn1 are more prominent in atrial than in ventricular cardiomyocytes. Disruption of NBCn1 expression lowers Na+,HCO3 --cotransport activity more than 50% in atria without significantly influencing net acid extrusion activity of ventricular cardiomyocytes. Loss of NBCn1 is associated with hypertension (blood pressure increased by ~15 mmHg), cardiac hypertrophy (heart/body weight increased by ~10%), and prolonged ventricular isovolumic relaxation time (increased by ~25%). NBCn1 knockout does not affect cardiomyocyte size, collagen content in the heart wall, overall cardiac contractile function, electrophysiological properties of ventricular cardiomyocytes, or the electrocardiogram.Conclusion: NBCn1 is a main mechanism of Na+,HCO3 --cotransport in atrial tissue and contributes substantially to net acid extrusion during intracellular acidification. NBCn1 does not play any major direct role in ventricular cardiomyocytes of unchallenged mice, but global knockout of NBCn1 increases systemic blood pressure and results in the development of cardiac hypertrophy.Fil: Espejo, María Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Orlowski, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Sørensen, Trine M.. University Aarhus; DinamarcaFil: Matchkov, Vladimir V.. University Aarhus; DinamarcaFil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Boedtkjer, Ebbe. University Aarhus; DinamarcaWiley Blackwell Publishing, Inc2025-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/282356Espejo, María Sofía; Orlowski, Alejandro; Sørensen, Trine M.; Matchkov, Vladimir V.; Aiello, Ernesto Alejandro; et al.; Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac Hypertrophy; Wiley Blackwell Publishing, Inc; Acta Physiologica; 241; 8; 7-2025; 1-121748-1708CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1111/apha.70078info:eu-repo/semantics/altIdentifier/doi/10.1111/apha.70078info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-03-11T12:06:33Zoai:ri.conicet.gov.ar:11336/282356instacron: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:34982026-03-11 12:06:33.485CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac Hypertrophy
title Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac Hypertrophy
spellingShingle Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac Hypertrophy
Espejo, María Sofía
Heart
Atria
Hypertrophy
NBCn1
title_short Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac Hypertrophy
title_full Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac Hypertrophy
title_fullStr Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac Hypertrophy
title_full_unstemmed Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac Hypertrophy
title_sort Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac Hypertrophy
dc.creator.none.fl_str_mv Espejo, María Sofía
Orlowski, Alejandro
Sørensen, Trine M.
Matchkov, Vladimir V.
Aiello, Ernesto Alejandro
Boedtkjer, Ebbe
author Espejo, María Sofía
author_facet Espejo, María Sofía
Orlowski, Alejandro
Sørensen, Trine M.
Matchkov, Vladimir V.
Aiello, Ernesto Alejandro
Boedtkjer, Ebbe
author_role author
author2 Orlowski, Alejandro
Sørensen, Trine M.
Matchkov, Vladimir V.
Aiello, Ernesto Alejandro
Boedtkjer, Ebbe
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Heart
Atria
Hypertrophy
NBCn1
topic Heart
Atria
Hypertrophy
NBCn1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Aim: Metabolic disturbances challenge pH homeostasis in cardiomyocytes. The electroneutral Na+,HCO3 --cotransporter NBCn1/Slc4a7 mediates net acid extrusion, and genetic variation in SLC4A7 contributes to human hypertension and cardiovascular risk. Nonetheless, the cardiac consequences of disrupted NBCn1 expression and function remain unclear. Here, we test the hypothesis that NBCn1, either directly or indirectly, influences cardiac structure, contractile function, and electrophysiological properties.Methods: Based on mice with global loss of NBCn1, we measure intracellular pH in atria and ventricles of the heart (fluorescence microscopy), membrane potential responses (patch clamping), electro- and echocardiographic variables, blood pressure (telemetry), and cardiac dimensions (in vivo and postmortem analyses).Results: We find that protein and mRNA expression of NBCn1 are more prominent in atrial than in ventricular cardiomyocytes. Disruption of NBCn1 expression lowers Na+,HCO3 --cotransport activity more than 50% in atria without significantly influencing net acid extrusion activity of ventricular cardiomyocytes. Loss of NBCn1 is associated with hypertension (blood pressure increased by ~15 mmHg), cardiac hypertrophy (heart/body weight increased by ~10%), and prolonged ventricular isovolumic relaxation time (increased by ~25%). NBCn1 knockout does not affect cardiomyocyte size, collagen content in the heart wall, overall cardiac contractile function, electrophysiological properties of ventricular cardiomyocytes, or the electrocardiogram.Conclusion: NBCn1 is a main mechanism of Na+,HCO3 --cotransport in atrial tissue and contributes substantially to net acid extrusion during intracellular acidification. NBCn1 does not play any major direct role in ventricular cardiomyocytes of unchallenged mice, but global knockout of NBCn1 increases systemic blood pressure and results in the development of cardiac hypertrophy.
Fil: Espejo, María Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Orlowski, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Sørensen, Trine M.. University Aarhus; Dinamarca
Fil: Matchkov, Vladimir V.. University Aarhus; Dinamarca
Fil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Boedtkjer, Ebbe. University Aarhus; Dinamarca
description Aim: Metabolic disturbances challenge pH homeostasis in cardiomyocytes. The electroneutral Na+,HCO3 --cotransporter NBCn1/Slc4a7 mediates net acid extrusion, and genetic variation in SLC4A7 contributes to human hypertension and cardiovascular risk. Nonetheless, the cardiac consequences of disrupted NBCn1 expression and function remain unclear. Here, we test the hypothesis that NBCn1, either directly or indirectly, influences cardiac structure, contractile function, and electrophysiological properties.Methods: Based on mice with global loss of NBCn1, we measure intracellular pH in atria and ventricles of the heart (fluorescence microscopy), membrane potential responses (patch clamping), electro- and echocardiographic variables, blood pressure (telemetry), and cardiac dimensions (in vivo and postmortem analyses).Results: We find that protein and mRNA expression of NBCn1 are more prominent in atrial than in ventricular cardiomyocytes. Disruption of NBCn1 expression lowers Na+,HCO3 --cotransport activity more than 50% in atria without significantly influencing net acid extrusion activity of ventricular cardiomyocytes. Loss of NBCn1 is associated with hypertension (blood pressure increased by ~15 mmHg), cardiac hypertrophy (heart/body weight increased by ~10%), and prolonged ventricular isovolumic relaxation time (increased by ~25%). NBCn1 knockout does not affect cardiomyocyte size, collagen content in the heart wall, overall cardiac contractile function, electrophysiological properties of ventricular cardiomyocytes, or the electrocardiogram.Conclusion: NBCn1 is a main mechanism of Na+,HCO3 --cotransport in atrial tissue and contributes substantially to net acid extrusion during intracellular acidification. NBCn1 does not play any major direct role in ventricular cardiomyocytes of unchallenged mice, but global knockout of NBCn1 increases systemic blood pressure and results in the development of cardiac hypertrophy.
publishDate 2025
dc.date.none.fl_str_mv 2025-07
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/11336/282356
Espejo, María Sofía; Orlowski, Alejandro; Sørensen, Trine M.; Matchkov, Vladimir V.; Aiello, Ernesto Alejandro; et al.; Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac Hypertrophy; Wiley Blackwell Publishing, Inc; Acta Physiologica; 241; 8; 7-2025; 1-12
1748-1708
CONICET Digital
CONICET
url http://hdl.handle.net/11336/282356
identifier_str_mv Espejo, María Sofía; Orlowski, Alejandro; Sørensen, Trine M.; Matchkov, Vladimir V.; Aiello, Ernesto Alejandro; et al.; Loss of Na + , HCO 3 − ‐Cotransporter NBCn1 Inhibits Net Acid Extrusion in the Atria and Causes Hypertension‐Associated Cardiac Hypertrophy; Wiley Blackwell Publishing, Inc; Acta Physiologica; 241; 8; 7-2025; 1-12
1748-1708
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1111/apha.70078
info:eu-repo/semantics/altIdentifier/doi/10.1111/apha.70078
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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 12.977003

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