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)...
| Autores: | , , , , , , , , |
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| 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 |
| Sumario: | 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. |
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