Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium

Autores
Netti, Vanina Alejandra; Pizzoni, Alejandro; Peréz Domínguez, Martha; Ford, Paula; Pasantes Morales, Herminia; Ramos Mandujano, Gerardo; Capurro, Claudia Graciela
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Neuronal activity in the retina generates osmotic gradients that lead to Müller cell swelling, followed by a regulatory volume decrease (RVD) response, partially due to the isoosmotic efflux of KCl and water. However, our previous studies in a human Müller cell line (MIO-M1) demonstrated that an important fraction of RVD may also involve the efflux of organic solutes. We also showed that RVD depends on the swelling-induced Ca 2+ release from intracellular stores. Here we investigate the contribution of taurine (Tau) and glutamate (Glu), the most relevant amino acids in Müller cells, to RVD through the volume-regulated anion channel (VRAC), as well as their Ca 2+ dependency in MIO-M1 cells. Swelling-induced [ 3 H]Tau/ [ 3 H]Glu release was assessed by radiotracer assays and cell volume by fluorescence videomicroscopy. Results showed that cells exhibited an osmosensitive efflux of [ 3 H]Tau and [ 3 H]Glu (Tau > Glu) blunted by VRAC inhibitors 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)-oxybutyric acid and carbenoxolone reducing RVD. Only [ 3 H]Tau efflux was mainly dependent on Ca 2+ release from intracellular stores. RVD was unaffected in a Ca 2+ -free medium, probably due to Ca 2+ -independent Tau and Glu release, but was reduced by chelating intracellular Ca 2+ . The inhibition of phosphatidylinositol-3-kinase reduced [ 3 H]Glu efflux but also the Ca 2+ -insensitive [ 3 H]Tau fraction and decreased RVD, providing evidence of the relevance of this Ca 2+ -independent pathway. We propose that VRAC-mediated Tau and Glu release has a relevant role in RVD in Müller cells. The observed disparities in Ca 2+ influence on amino acid release suggest the presence of VRAC isoforms that may differ in substrate selectivity and regulatory mechanisms, with important implications for retinal physiology. NEW & NOTEWORTHY The mechanisms for cell volume regulation in retinal Müller cells are still unknown. We show that swelling-induced taurine and glutamate release mediated by the volume-regulated anion channel (VRAC) largely contributes the to the regu- latory volume decrease response in a human Müller cell line. Interestingly, the hypotonic-induced efflux of these amino acids exhibits disparities in Ca 2+ -dependent and-independent regulatory mechanisms, which strongly suggests that Müller cells may express different VRAC heteromers formed by the recently discovered leu-cine-rich repeat containing 8 (LRRC8) proteins.
Fil: Netti, Vanina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Pizzoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Peréz Domínguez, Martha. Universidad Nacional Autónoma de México; México
Fil: Ford, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Pasantes Morales, Herminia. Universidad Nacional Autónoma de México; México
Fil: Ramos Mandujano, Gerardo. Universidad Nacional Autónoma de México; México
Fil: Capurro, Claudia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Materia
CELL VOLUME REGULATION
GLUTAMATE
HUMAN MÜLLER CELLS
TAURINE
VOLUME-REGULATED ANION CHANNEL
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:11336/88380
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/88380
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calciumNetti, Vanina AlejandraPizzoni, AlejandroPeréz Domínguez, MarthaFord, PaulaPasantes Morales, HerminiaRamos Mandujano, GerardoCapurro, Claudia GracielaCELL VOLUME REGULATIONGLUTAMATEHUMAN MÜLLER CELLSTAURINEVOLUME-REGULATED ANION CHANNELhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Neuronal activity in the retina generates osmotic gradients that lead to Müller cell swelling, followed by a regulatory volume decrease (RVD) response, partially due to the isoosmotic efflux of KCl and water. However, our previous studies in a human Müller cell line (MIO-M1) demonstrated that an important fraction of RVD may also involve the efflux of organic solutes. We also showed that RVD depends on the swelling-induced Ca 2+ release from intracellular stores. Here we investigate the contribution of taurine (Tau) and glutamate (Glu), the most relevant amino acids in Müller cells, to RVD through the volume-regulated anion channel (VRAC), as well as their Ca 2+ dependency in MIO-M1 cells. Swelling-induced [ 3 H]Tau/ [ 3 H]Glu release was assessed by radiotracer assays and cell volume by fluorescence videomicroscopy. Results showed that cells exhibited an osmosensitive efflux of [ 3 H]Tau and [ 3 H]Glu (Tau > Glu) blunted by VRAC inhibitors 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)-oxybutyric acid and carbenoxolone reducing RVD. Only [ 3 H]Tau efflux was mainly dependent on Ca 2+ release from intracellular stores. RVD was unaffected in a Ca 2+ -free medium, probably due to Ca 2+ -independent Tau and Glu release, but was reduced by chelating intracellular Ca 2+ . The inhibition of phosphatidylinositol-3-kinase reduced [ 3 H]Glu efflux but also the Ca 2+ -insensitive [ 3 H]Tau fraction and decreased RVD, providing evidence of the relevance of this Ca 2+ -independent pathway. We propose that VRAC-mediated Tau and Glu release has a relevant role in RVD in Müller cells. The observed disparities in Ca 2+ influence on amino acid release suggest the presence of VRAC isoforms that may differ in substrate selectivity and regulatory mechanisms, with important implications for retinal physiology. NEW & NOTEWORTHY The mechanisms for cell volume regulation in retinal Müller cells are still unknown. We show that swelling-induced taurine and glutamate release mediated by the volume-regulated anion channel (VRAC) largely contributes the to the regu- latory volume decrease response in a human Müller cell line. Interestingly, the hypotonic-induced efflux of these amino acids exhibits disparities in Ca 2+ -dependent and-independent regulatory mechanisms, which strongly suggests that Müller cells may express different VRAC heteromers formed by the recently discovered leu-cine-rich repeat containing 8 (LRRC8) proteins.Fil: Netti, Vanina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Pizzoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Peréz Domínguez, Martha. Universidad Nacional Autónoma de México; MéxicoFil: Ford, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Pasantes Morales, Herminia. Universidad Nacional Autónoma de México; MéxicoFil: Ramos Mandujano, Gerardo. Universidad Nacional Autónoma de México; MéxicoFil: Capurro, Claudia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaAmerican Physiological Society2018-09info: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/11336/88380Netti, Vanina Alejandra; Pizzoni, Alejandro; Peréz Domínguez, Martha; Ford, Paula; Pasantes Morales, Herminia; et al.; Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium; American Physiological Society; Journal of Neurophysiology; 120; 3; 9-2018; 973-9840022-3077CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/10.1152/jn.00725.2017info:eu-repo/semantics/altIdentifier/doi/10.1152/jn.00725.2017info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:23Zoai:ri.conicet.gov.ar:11336/88380instacron: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 09:46:23.995CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium
title Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium
spellingShingle Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium
Netti, Vanina Alejandra
CELL VOLUME REGULATION
GLUTAMATE
HUMAN MÜLLER CELLS
TAURINE
VOLUME-REGULATED ANION CHANNEL
title_short Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium
title_full Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium
title_fullStr Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium
title_full_unstemmed Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium
title_sort Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium
dc.creator.none.fl_str_mv Netti, Vanina Alejandra
Pizzoni, Alejandro
Peréz Domínguez, Martha
Ford, Paula
Pasantes Morales, Herminia
Ramos Mandujano, Gerardo
Capurro, Claudia Graciela
author Netti, Vanina Alejandra
author_facet Netti, Vanina Alejandra
Pizzoni, Alejandro
Peréz Domínguez, Martha
Ford, Paula
Pasantes Morales, Herminia
Ramos Mandujano, Gerardo
Capurro, Claudia Graciela
author_role author
author2 Pizzoni, Alejandro
Peréz Domínguez, Martha
Ford, Paula
Pasantes Morales, Herminia
Ramos Mandujano, Gerardo
Capurro, Claudia Graciela
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CELL VOLUME REGULATION
GLUTAMATE
HUMAN MÜLLER CELLS
TAURINE
VOLUME-REGULATED ANION CHANNEL
topic CELL VOLUME REGULATION
GLUTAMATE
HUMAN MÜLLER CELLS
TAURINE
VOLUME-REGULATED ANION CHANNEL
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Neuronal activity in the retina generates osmotic gradients that lead to Müller cell swelling, followed by a regulatory volume decrease (RVD) response, partially due to the isoosmotic efflux of KCl and water. However, our previous studies in a human Müller cell line (MIO-M1) demonstrated that an important fraction of RVD may also involve the efflux of organic solutes. We also showed that RVD depends on the swelling-induced Ca 2+ release from intracellular stores. Here we investigate the contribution of taurine (Tau) and glutamate (Glu), the most relevant amino acids in Müller cells, to RVD through the volume-regulated anion channel (VRAC), as well as their Ca 2+ dependency in MIO-M1 cells. Swelling-induced [ 3 H]Tau/ [ 3 H]Glu release was assessed by radiotracer assays and cell volume by fluorescence videomicroscopy. Results showed that cells exhibited an osmosensitive efflux of [ 3 H]Tau and [ 3 H]Glu (Tau > Glu) blunted by VRAC inhibitors 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)-oxybutyric acid and carbenoxolone reducing RVD. Only [ 3 H]Tau efflux was mainly dependent on Ca 2+ release from intracellular stores. RVD was unaffected in a Ca 2+ -free medium, probably due to Ca 2+ -independent Tau and Glu release, but was reduced by chelating intracellular Ca 2+ . The inhibition of phosphatidylinositol-3-kinase reduced [ 3 H]Glu efflux but also the Ca 2+ -insensitive [ 3 H]Tau fraction and decreased RVD, providing evidence of the relevance of this Ca 2+ -independent pathway. We propose that VRAC-mediated Tau and Glu release has a relevant role in RVD in Müller cells. The observed disparities in Ca 2+ influence on amino acid release suggest the presence of VRAC isoforms that may differ in substrate selectivity and regulatory mechanisms, with important implications for retinal physiology. NEW & NOTEWORTHY The mechanisms for cell volume regulation in retinal Müller cells are still unknown. We show that swelling-induced taurine and glutamate release mediated by the volume-regulated anion channel (VRAC) largely contributes the to the regu- latory volume decrease response in a human Müller cell line. Interestingly, the hypotonic-induced efflux of these amino acids exhibits disparities in Ca 2+ -dependent and-independent regulatory mechanisms, which strongly suggests that Müller cells may express different VRAC heteromers formed by the recently discovered leu-cine-rich repeat containing 8 (LRRC8) proteins.
Fil: Netti, Vanina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Pizzoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Peréz Domínguez, Martha. Universidad Nacional Autónoma de México; México
Fil: Ford, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Pasantes Morales, Herminia. Universidad Nacional Autónoma de México; México
Fil: Ramos Mandujano, Gerardo. Universidad Nacional Autónoma de México; México
Fil: Capurro, Claudia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
description Neuronal activity in the retina generates osmotic gradients that lead to Müller cell swelling, followed by a regulatory volume decrease (RVD) response, partially due to the isoosmotic efflux of KCl and water. However, our previous studies in a human Müller cell line (MIO-M1) demonstrated that an important fraction of RVD may also involve the efflux of organic solutes. We also showed that RVD depends on the swelling-induced Ca 2+ release from intracellular stores. Here we investigate the contribution of taurine (Tau) and glutamate (Glu), the most relevant amino acids in Müller cells, to RVD through the volume-regulated anion channel (VRAC), as well as their Ca 2+ dependency in MIO-M1 cells. Swelling-induced [ 3 H]Tau/ [ 3 H]Glu release was assessed by radiotracer assays and cell volume by fluorescence videomicroscopy. Results showed that cells exhibited an osmosensitive efflux of [ 3 H]Tau and [ 3 H]Glu (Tau > Glu) blunted by VRAC inhibitors 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)-oxybutyric acid and carbenoxolone reducing RVD. Only [ 3 H]Tau efflux was mainly dependent on Ca 2+ release from intracellular stores. RVD was unaffected in a Ca 2+ -free medium, probably due to Ca 2+ -independent Tau and Glu release, but was reduced by chelating intracellular Ca 2+ . The inhibition of phosphatidylinositol-3-kinase reduced [ 3 H]Glu efflux but also the Ca 2+ -insensitive [ 3 H]Tau fraction and decreased RVD, providing evidence of the relevance of this Ca 2+ -independent pathway. We propose that VRAC-mediated Tau and Glu release has a relevant role in RVD in Müller cells. The observed disparities in Ca 2+ influence on amino acid release suggest the presence of VRAC isoforms that may differ in substrate selectivity and regulatory mechanisms, with important implications for retinal physiology. NEW & NOTEWORTHY The mechanisms for cell volume regulation in retinal Müller cells are still unknown. We show that swelling-induced taurine and glutamate release mediated by the volume-regulated anion channel (VRAC) largely contributes the to the regu- latory volume decrease response in a human Müller cell line. Interestingly, the hypotonic-induced efflux of these amino acids exhibits disparities in Ca 2+ -dependent and-independent regulatory mechanisms, which strongly suggests that Müller cells may express different VRAC heteromers formed by the recently discovered leu-cine-rich repeat containing 8 (LRRC8) proteins.
publishDate 2018
dc.date.none.fl_str_mv 2018-09
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/11336/88380
Netti, Vanina Alejandra; Pizzoni, Alejandro; Peréz Domínguez, Martha; Ford, Paula; Pasantes Morales, Herminia; et al.; Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium; American Physiological Society; Journal of Neurophysiology; 120; 3; 9-2018; 973-984
0022-3077
CONICET Digital
CONICET
url http://hdl.handle.net/11336/88380
identifier_str_mv Netti, Vanina Alejandra; Pizzoni, Alejandro; Peréz Domínguez, Martha; Ford, Paula; Pasantes Morales, Herminia; et al.; Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: Differences in modulation by calcium; American Physiological Society; Journal of Neurophysiology; 120; 3; 9-2018; 973-984
0022-3077
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://www.physiology.org/doi/10.1152/jn.00725.2017
info:eu-repo/semantics/altIdentifier/doi/10.1152/jn.00725.2017
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
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 13.13397

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