Intracellular signalling in arterial chemoreceptors during acute hypoxia and glucose deprivation: role of ATP

The carotid body (CB) is the main oxygen (O2) sensing organ that mediates reflex hyperventilation and increased cardiac output in response to hypoxaemia. Acute O2 sensing is an intrinsic property of CB glomus cells, which contain special mitochondria to generate signalling molecules (NADH and H2O2)...

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Autores: Torres López, María, González-Rodríguez, Patricia, Colinas, Olaia, Rho, Hee Sool, Torres-Torrelo, Hortensia, Castellano, Antonio, Gao, Lin, Ortega-Sáenz, Patricia, López-Barneo, José
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/391023
Acceso en línea:http://hdl.handle.net/10261/391023
https://api.elsevier.com/content/abstract/scopus_id/85219569553
Access Level:acceso abierto
Palabra clave:H2O2
NADH
TASK3 channels
Acute oxygen sensing
Carotid body glomus cells
Cytosolic ATP
Electron transport chain inhibitors
Glucose sensing
Hypoxia
Mitochondria‐to‐membrane signalling
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oai_identifier_str oai:digital.csic.es:10261/391023
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Intracellular signalling in arterial chemoreceptors during acute hypoxia and glucose deprivation: role of ATP
title Intracellular signalling in arterial chemoreceptors during acute hypoxia and glucose deprivation: role of ATP
spellingShingle Intracellular signalling in arterial chemoreceptors during acute hypoxia and glucose deprivation: role of ATP
Torres López, María
H2O2
NADH
TASK3 channels
Acute oxygen sensing
Carotid body glomus cells
Cytosolic ATP
Electron transport chain inhibitors
Glucose sensing
Hypoxia
Mitochondria‐to‐membrane signalling
title_short Intracellular signalling in arterial chemoreceptors during acute hypoxia and glucose deprivation: role of ATP
title_full Intracellular signalling in arterial chemoreceptors during acute hypoxia and glucose deprivation: role of ATP
title_fullStr Intracellular signalling in arterial chemoreceptors during acute hypoxia and glucose deprivation: role of ATP
title_full_unstemmed Intracellular signalling in arterial chemoreceptors during acute hypoxia and glucose deprivation: role of ATP
title_sort Intracellular signalling in arterial chemoreceptors during acute hypoxia and glucose deprivation: role of ATP
dc.creator.none.fl_str_mv Torres López, María
González-Rodríguez, Patricia
Colinas, Olaia
Rho, Hee Sool
Torres-Torrelo, Hortensia
Castellano, Antonio
Gao, Lin
Ortega-Sáenz, Patricia
López-Barneo, José
author Torres López, María
author_facet Torres López, María
González-Rodríguez, Patricia
Colinas, Olaia
Rho, Hee Sool
Torres-Torrelo, Hortensia
Castellano, Antonio
Gao, Lin
Ortega-Sáenz, Patricia
López-Barneo, José
author_role author
author2 González-Rodríguez, Patricia
Colinas, Olaia
Rho, Hee Sool
Torres-Torrelo, Hortensia
Castellano, Antonio
Gao, Lin
Ortega-Sáenz, Patricia
López-Barneo, José
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
European Commission
Torres López, María [0000-0001-6569-0397]
González-Rodríguez, Patricia [0000-0002-2561-3984]
Colinas, Olaia [0000-0002-1190-0157]
Rho, Hee Sool [0000-0002-1688-3237]
Torres-Torrelo, Hortensia [0000-0001-5770-6002]
Castellano, Antonio [0000-0003-3955-5137]
Ortega-Sáenz, Patricia [0000-0003-4962-8483]
López-Barneo, José [0000-0003-4101-6095]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv H2O2
NADH
TASK3 channels
Acute oxygen sensing
Carotid body glomus cells
Cytosolic ATP
Electron transport chain inhibitors
Glucose sensing
Hypoxia
Mitochondria‐to‐membrane signalling
topic H2O2
NADH
TASK3 channels
Acute oxygen sensing
Carotid body glomus cells
Cytosolic ATP
Electron transport chain inhibitors
Glucose sensing
Hypoxia
Mitochondria‐to‐membrane signalling
description The carotid body (CB) is the main oxygen (O2) sensing organ that mediates reflex hyperventilation and increased cardiac output in response to hypoxaemia. Acute O2 sensing is an intrinsic property of CB glomus cells, which contain special mitochondria to generate signalling molecules (NADH and H2O2) that modulate membrane K+ channels in response to lowered O2 tension (hypoxia). In parallel with these membrane-associated events, glomus cells are highly sensitive to mitochondrial electron transport chain (ETC) inhibitors. It was suggested that a decrease in oxidative production of ATP is a critical event mediating hypoxia-induced cell depolarization. Here, we show that rotenone [an inhibitor of mitochondrial complex (MC) I] activates rat and mouse glomus cells but abolishes their responsiveness to hypoxia. Rotenone does not prevent further activation of the cells by cyanide (a blocker of MCIV) or glucose deprivation. Responsiveness to glucose deprivation is enhanced in O2-insenstive glomus cells with genetic disruption of MCI. These findings suggest that acute O2 sensing requires a functional MCI but that a decrease in intracellular ATP, presumably produced by the simultaneous inhibition of MCI and MCIV, is not involved in hypoxia signalling. In support of this concept, ATP levels in single glomus cells were unaltered by hypoxia, but rapidly declined following exposure of the cells to low glucose or to inhibitors of oxidative phosphorylation. These observations indicate that a reduction in intracellular ATP does not participate in physiological acute O2 sensing. However, local decreases in ATP of glycolytic origin may contribute to low glucose signalling in glomus cells. KEY POINTS: The carotid body contains oxygen-sensitive glomus cells with specialized mitochondria that generate signalling molecules (NADH and H2O2) to inhibit membrane K+ channels in response to hypoxia. Glomus cells are highly sensitive to electron transport chain (ETC) blockers. It was suggested that a decrease in intracellular ATP is the main signal inducing K+ channel inhibition and depolarization in response to hypoxia or ETC blockade. Rotenone, an inhibitor of mitochondrial complex (MC) I, activates glomus cells but abolishes their responsiveness to hypoxia. However, rotenone does not prevent further activation of glomus cells by cyanide (an MCIV blocker) or glucose deprivation. Single-cell ATP levels were unaltered by hypoxia, but decreased rapidly following exposure of glomus cells to 0 mM glucose or inhibitors of oxidative phosphorylation. A reduction in intracellular ATP does not participate in signalling acute hypoxia. However, it may contribute to hypoglycaemia signalling in glomus cells.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
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Publisher's version
info:eu-repo/semantics/publishedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/391023
https://api.elsevier.com/content/abstract/scopus_id/85219569553
url http://hdl.handle.net/10261/391023
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dc.language.none.fl_str_mv Inglés
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The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI http://dx.doi.org/10.1113/JP287130
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dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Intracellular signalling in arterial chemoreceptors during acute hypoxia and glucose deprivation: role of ATPTorres López, MaríaGonzález-Rodríguez, PatriciaColinas, OlaiaRho, Hee SoolTorres-Torrelo, HortensiaCastellano, AntonioGao, LinOrtega-Sáenz, PatriciaLópez-Barneo, JoséH2O2NADHTASK3 channelsAcute oxygen sensingCarotid body glomus cellsCytosolic ATPElectron transport chain inhibitorsGlucose sensingHypoxiaMitochondria‐to‐membrane signallingThe carotid body (CB) is the main oxygen (O2) sensing organ that mediates reflex hyperventilation and increased cardiac output in response to hypoxaemia. Acute O2 sensing is an intrinsic property of CB glomus cells, which contain special mitochondria to generate signalling molecules (NADH and H2O2) that modulate membrane K+ channels in response to lowered O2 tension (hypoxia). In parallel with these membrane-associated events, glomus cells are highly sensitive to mitochondrial electron transport chain (ETC) inhibitors. It was suggested that a decrease in oxidative production of ATP is a critical event mediating hypoxia-induced cell depolarization. Here, we show that rotenone [an inhibitor of mitochondrial complex (MC) I] activates rat and mouse glomus cells but abolishes their responsiveness to hypoxia. Rotenone does not prevent further activation of the cells by cyanide (a blocker of MCIV) or glucose deprivation. Responsiveness to glucose deprivation is enhanced in O2-insenstive glomus cells with genetic disruption of MCI. These findings suggest that acute O2 sensing requires a functional MCI but that a decrease in intracellular ATP, presumably produced by the simultaneous inhibition of MCI and MCIV, is not involved in hypoxia signalling. In support of this concept, ATP levels in single glomus cells were unaltered by hypoxia, but rapidly declined following exposure of the cells to low glucose or to inhibitors of oxidative phosphorylation. These observations indicate that a reduction in intracellular ATP does not participate in physiological acute O2 sensing. However, local decreases in ATP of glycolytic origin may contribute to low glucose signalling in glomus cells. KEY POINTS: The carotid body contains oxygen-sensitive glomus cells with specialized mitochondria that generate signalling molecules (NADH and H2O2) to inhibit membrane K+ channels in response to hypoxia. Glomus cells are highly sensitive to electron transport chain (ETC) blockers. It was suggested that a decrease in intracellular ATP is the main signal inducing K+ channel inhibition and depolarization in response to hypoxia or ETC blockade. Rotenone, an inhibitor of mitochondrial complex (MC) I, activates glomus cells but abolishes their responsiveness to hypoxia. However, rotenone does not prevent further activation of glomus cells by cyanide (an MCIV blocker) or glucose deprivation. Single-cell ATP levels were unaltered by hypoxia, but decreased rapidly following exposure of glomus cells to 0 mM glucose or inhibitors of oxidative phosphorylation. A reduction in intracellular ATP does not participate in signalling acute hypoxia. However, it may contribute to hypoglycaemia signalling in glomus cells.This research was supported by Spanish Ministries of Science and Innovation and Health (Grants PID2019-106410RB-I00, PID2019-110817R, PID2022-138131OB-I00 and PID2023-146862OB-100 funded by MCIN/AEI/10.13039/501100011033 to J.L.-B., L.G. and P.O.-S) and the European Research Council (ERC Advanced Grant PRJ201502629).Peer reviewedJohn Wiley & SonsMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)European CommissionTorres López, María [0000-0001-6569-0397]González-Rodríguez, Patricia [0000-0002-2561-3984]Colinas, Olaia [0000-0002-1190-0157]Rho, Hee Sool [0000-0002-1688-3237]Torres-Torrelo, Hortensia [0000-0001-5770-6002]Castellano, Antonio [0000-0003-3955-5137]Ortega-Sáenz, Patricia [0000-0003-4962-8483]López-Barneo, José [0000-0003-4101-6095]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/391023https://api.elsevier.com/content/abstract/scopus_id/85219569553reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-106410RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110817RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-138131OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-146862OB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI http://dx.doi.org/10.1113/JP287130Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3910232026-05-22T06:33:51Z
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