Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools

Autores
de Giusti, Verónica Celeste; Orlowski, Alejandro; Villa-Abrille, María Celeste; Chiappe, Gladys Ethel; Casey, Joseph R.; Alvarez, Bernardo; Aiello, Ernesto Alejandro
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND AND PURPOSE Na +/HCO 3 - co-transport (NBC) regulates intracellular pH (pH i) in the heart. We have studied the electrogenic NBC isoform NBCe1 by examining the effect of functional antibodies to this protein. EXPERIMENTAL APPROACH We generated two antibodies against putative extracellular loop domains 3 (a-L3) and 4 (a-L4) of NBCe1 which recognized NBCe1 on immunoblots and immunostaining experiments. pH i was monitored using epi-fluorescence measurements in cat ventricular myocytes. Transport activity of total NBC and of NBCe1 in isolation were evaluated after an ammonium ion-induced acidosis (expressed as H + flux, J H, in mmol·L -1 min -1 at pH i 6.8) and during membrane depolarization with high extracellular potassium (potassium pulse, expressed as ΔpH i) respectively. KEY RESULTS The potassium pulse produced a pH i increase of 0.18 ± 0.006 (n= 5), which was reduced by the a-L3 antibody (0.016 ± 0.019). The a-L-3 also decreased J H by 50%. Surprisingly, during the potassium pulse, a-L4 induced a higher pH i increase than control,(0.25 ± 0.018) whereas the recovery of pH i from acidosis was faster (J H was almost double the control value). In perforated-patch experiments, a-L3 prolonged and a-L4 shortened action potential duration, consistent with blockade and stimulation of NBCe1-carried anionic current respectively. CONCLUSIONS AND IMPLICATIONS Both antibodies recognized NBCe1, but they had opposing effects on the function of this transporter, as the a-L3 was inhibitory and the a-L4 was excitatory. These antibodies could be valuable in studies on the pathophysiology of NBCe1 in cardiac tissue, opening a path for their potential clinical use. © 2011 The Authors.
Fil: de Giusti, Verónica Celeste. 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: Villa-Abrille, María Celeste. 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: Chiappe, Gladys Ethel. 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: Casey, Joseph R.. University of Alberta; Canadá
Fil: Alvarez, Bernardo. 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: 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
Materia
Cardiac Myocytes
Functional Antibodies
Na +/Hco 3 - Co-Transporter
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:11336/61760
Acceder
id CONICETDig_50fcfcf2111eace1140cf4bb57b8f5ef
oai_identifier_str oai:ri.conicet.gov.ar:11336/61760
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological toolsde Giusti, Verónica CelesteOrlowski, AlejandroVilla-Abrille, María CelesteChiappe, Gladys EthelCasey, Joseph R.Alvarez, BernardoAiello, Ernesto AlejandroCardiac MyocytesFunctional AntibodiesNa +/Hco 3 - Co-Transporterhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3BACKGROUND AND PURPOSE Na +/HCO 3 - co-transport (NBC) regulates intracellular pH (pH i) in the heart. We have studied the electrogenic NBC isoform NBCe1 by examining the effect of functional antibodies to this protein. EXPERIMENTAL APPROACH We generated two antibodies against putative extracellular loop domains 3 (a-L3) and 4 (a-L4) of NBCe1 which recognized NBCe1 on immunoblots and immunostaining experiments. pH i was monitored using epi-fluorescence measurements in cat ventricular myocytes. Transport activity of total NBC and of NBCe1 in isolation were evaluated after an ammonium ion-induced acidosis (expressed as H + flux, J H, in mmol·L -1 min -1 at pH i 6.8) and during membrane depolarization with high extracellular potassium (potassium pulse, expressed as ΔpH i) respectively. KEY RESULTS The potassium pulse produced a pH i increase of 0.18 ± 0.006 (n= 5), which was reduced by the a-L3 antibody (0.016 ± 0.019). The a-L-3 also decreased J H by 50%. Surprisingly, during the potassium pulse, a-L4 induced a higher pH i increase than control,(0.25 ± 0.018) whereas the recovery of pH i from acidosis was faster (J H was almost double the control value). In perforated-patch experiments, a-L3 prolonged and a-L4 shortened action potential duration, consistent with blockade and stimulation of NBCe1-carried anionic current respectively. CONCLUSIONS AND IMPLICATIONS Both antibodies recognized NBCe1, but they had opposing effects on the function of this transporter, as the a-L3 was inhibitory and the a-L4 was excitatory. These antibodies could be valuable in studies on the pathophysiology of NBCe1 in cardiac tissue, opening a path for their potential clinical use. © 2011 The Authors.Fil: de Giusti, Verónica Celeste. 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: Villa-Abrille, María Celeste. 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: Chiappe, Gladys Ethel. 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: Casey, Joseph R.. University of Alberta; CanadáFil: Alvarez, Bernardo. 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: 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"; ArgentinaWiley Blackwell Publishing, Inc2011-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/61760de Giusti, Verónica Celeste; Orlowski, Alejandro; Villa-Abrille, María Celeste; Chiappe, Gladys Ethel; Casey, Joseph R.; et al.; Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools; Wiley Blackwell Publishing, Inc; British Journal of Pharmacology; 164; 8; 12-2011; 1976-19890007-1188CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1476-5381.2011.01496.xinfo:eu-repo/semantics/altIdentifier/url/https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1476-5381.2011.01496.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:41Zoai:ri.conicet.gov.ar:11336/61760instacron: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:34982025-09-03 09:59:41.34CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools
title Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools
spellingShingle Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools
de Giusti, Verónica Celeste
Cardiac Myocytes
Functional Antibodies
Na +/Hco 3 - Co-Transporter
title_short Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools
title_full Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools
title_fullStr Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools
title_full_unstemmed Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools
title_sort Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools
dc.creator.none.fl_str_mv de Giusti, Verónica Celeste
Orlowski, Alejandro
Villa-Abrille, María Celeste
Chiappe, Gladys Ethel
Casey, Joseph R.
Alvarez, Bernardo
Aiello, Ernesto Alejandro
author de Giusti, Verónica Celeste
author_facet de Giusti, Verónica Celeste
Orlowski, Alejandro
Villa-Abrille, María Celeste
Chiappe, Gladys Ethel
Casey, Joseph R.
Alvarez, Bernardo
Aiello, Ernesto Alejandro
author_role author
author2 Orlowski, Alejandro
Villa-Abrille, María Celeste
Chiappe, Gladys Ethel
Casey, Joseph R.
Alvarez, Bernardo
Aiello, Ernesto Alejandro
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Cardiac Myocytes
Functional Antibodies
Na +/Hco 3 - Co-Transporter
topic Cardiac Myocytes
Functional Antibodies
Na +/Hco 3 - Co-Transporter
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BACKGROUND AND PURPOSE Na +/HCO 3 - co-transport (NBC) regulates intracellular pH (pH i) in the heart. We have studied the electrogenic NBC isoform NBCe1 by examining the effect of functional antibodies to this protein. EXPERIMENTAL APPROACH We generated two antibodies against putative extracellular loop domains 3 (a-L3) and 4 (a-L4) of NBCe1 which recognized NBCe1 on immunoblots and immunostaining experiments. pH i was monitored using epi-fluorescence measurements in cat ventricular myocytes. Transport activity of total NBC and of NBCe1 in isolation were evaluated after an ammonium ion-induced acidosis (expressed as H + flux, J H, in mmol·L -1 min -1 at pH i 6.8) and during membrane depolarization with high extracellular potassium (potassium pulse, expressed as ΔpH i) respectively. KEY RESULTS The potassium pulse produced a pH i increase of 0.18 ± 0.006 (n= 5), which was reduced by the a-L3 antibody (0.016 ± 0.019). The a-L-3 also decreased J H by 50%. Surprisingly, during the potassium pulse, a-L4 induced a higher pH i increase than control,(0.25 ± 0.018) whereas the recovery of pH i from acidosis was faster (J H was almost double the control value). In perforated-patch experiments, a-L3 prolonged and a-L4 shortened action potential duration, consistent with blockade and stimulation of NBCe1-carried anionic current respectively. CONCLUSIONS AND IMPLICATIONS Both antibodies recognized NBCe1, but they had opposing effects on the function of this transporter, as the a-L3 was inhibitory and the a-L4 was excitatory. These antibodies could be valuable in studies on the pathophysiology of NBCe1 in cardiac tissue, opening a path for their potential clinical use. © 2011 The Authors.
Fil: de Giusti, Verónica Celeste. 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: Villa-Abrille, María Celeste. 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: Chiappe, Gladys Ethel. 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: Casey, Joseph R.. University of Alberta; Canadá
Fil: Alvarez, Bernardo. 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: 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
description BACKGROUND AND PURPOSE Na +/HCO 3 - co-transport (NBC) regulates intracellular pH (pH i) in the heart. We have studied the electrogenic NBC isoform NBCe1 by examining the effect of functional antibodies to this protein. EXPERIMENTAL APPROACH We generated two antibodies against putative extracellular loop domains 3 (a-L3) and 4 (a-L4) of NBCe1 which recognized NBCe1 on immunoblots and immunostaining experiments. pH i was monitored using epi-fluorescence measurements in cat ventricular myocytes. Transport activity of total NBC and of NBCe1 in isolation were evaluated after an ammonium ion-induced acidosis (expressed as H + flux, J H, in mmol·L -1 min -1 at pH i 6.8) and during membrane depolarization with high extracellular potassium (potassium pulse, expressed as ΔpH i) respectively. KEY RESULTS The potassium pulse produced a pH i increase of 0.18 ± 0.006 (n= 5), which was reduced by the a-L3 antibody (0.016 ± 0.019). The a-L-3 also decreased J H by 50%. Surprisingly, during the potassium pulse, a-L4 induced a higher pH i increase than control,(0.25 ± 0.018) whereas the recovery of pH i from acidosis was faster (J H was almost double the control value). In perforated-patch experiments, a-L3 prolonged and a-L4 shortened action potential duration, consistent with blockade and stimulation of NBCe1-carried anionic current respectively. CONCLUSIONS AND IMPLICATIONS Both antibodies recognized NBCe1, but they had opposing effects on the function of this transporter, as the a-L3 was inhibitory and the a-L4 was excitatory. These antibodies could be valuable in studies on the pathophysiology of NBCe1 in cardiac tissue, opening a path for their potential clinical use. © 2011 The Authors.
publishDate 2011
dc.date.none.fl_str_mv 2011-12
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/11336/61760
de Giusti, Verónica Celeste; Orlowski, Alejandro; Villa-Abrille, María Celeste; Chiappe, Gladys Ethel; Casey, Joseph R.; et al.; Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools; Wiley Blackwell Publishing, Inc; British Journal of Pharmacology; 164; 8; 12-2011; 1976-1989
0007-1188
CONICET Digital
CONICET
url http://hdl.handle.net/11336/61760
identifier_str_mv de Giusti, Verónica Celeste; Orlowski, Alejandro; Villa-Abrille, María Celeste; Chiappe, Gladys Ethel; Casey, Joseph R.; et al.; Antibodies against the cardiac sodium/bicarbonate co-transporter (NBCe1) as pharmacological tools; Wiley Blackwell Publishing, Inc; British Journal of Pharmacology; 164; 8; 12-2011; 1976-1989
0007-1188
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1476-5381.2011.01496.x
info:eu-repo/semantics/altIdentifier/url/https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1476-5381.2011.01496.x
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
application/pdf
application/pdf
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
_version_ 1842269595222671360
score 13.13397

Publicaciones similares