Carotid Body Physiology and Chemosensory Mechanisms

The carotid bodies are paired peripheral chemoreceptor organs located at the bifurcation of the common carotid arteries and serve as the principal detectors of arterial oxygen, carbon dioxide and pH. Within each body, specialised glomus (type I) cells sense changes in blood gases via mitochondrial and ion‐channel mediated pathways, leading to depolarisation, calcium influx and release of neurotransmitters. These chemical signals excite afferent fibres of the carotid sinus nerve, which project to brainstem respiratory and autonomic centres to regulate ventilation and sympathetic outflow. Surrounding type I cells, type II sustentacular cells exhibit glial-like properties and modulate synaptic transmission through paracrine release of ATP and other gliotransmitters. Acute hypoxia triggers rapid ventilatory reflexes, whereas chronic hypoxia drives cellular proliferation and plasticity through hypoxia-inducible factors, notably HIF-2α, reshaping chemosensitivity over days to weeks. Beyond classical respiratory control, the carotid body influences cardiovascular homeostasis, metabolic regulation and glucose tolerance, and its dysregulation contributes to hypertension, sleep apnoea and metabolic syndrome. Recent advances have elucidated molecular oxygen-sensing mechanisms, synaptic organisation at the tripartite chemosensory synapse and plastic responses, highlighting the carotid body as both a diagnostic indicator and a potential therapeutic target in cardiorespiratory and metabolic disorders.

Research from Nature Portfolio

Recent studies have identified mitochondrial NADH dehydrogenase activity as indispensable for acute oxygen sensing in glomus cells. In mitochondrial complex I-deficient models, reintroduction of a single-molecule yeast NADH oxidoreductase restored both the hypoxic ventilatory response and glomus cell oxygen sensitivity without rescuing proton-pumping capacity, demonstrating that electron transport rather than proton flux underpins chemoreception. This work clarifies the bioenergetic basis of arterial chemoreception and suggests gene-therapy approaches to correct mitochondrial defects in respiratory disorders. Foundational work in hypertensive models has shown that selective de-afferentation or denervation of the carotid body attenuates sympathetic overactivity and lowers arterial pressure in neurogenic hypertension. By resetting baroreflex function and reducing renal sympathetic nerve activity, targeting carotid body afferents offers a sustained antihypertensive strategy, paving the way for clinical approaches to resistant hypertension.

Carotid Body Physiology and Chemosensory Mechanisms publication trend

The graph below shows the total number of articles in carotid body physiology and chemosensory mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Glomus (type I) cell: Oxygen-sensitive chemoreceptor cell in the carotid body that releases neurotransmitters upon hypoxia.

Type II cell: Sustentacular cell with glial-like functions that modulates chemosensory transmission via gliotransmitters.

Hypoxic ventilatory response: Reflex increase in ventilation triggered by low arterial oxygen detected by carotid bodies.

Mitochondrial complex I: Multi-subunit enzyme of the electron transport chain essential for NADH oxidation and oxygen sensing.

Hypoxia-inducible factor 2α (HIF-2α): Transcription factor that drives expression of genes conferring oxygen chemosensitivity and adaptive proliferation.

Carotid sinus nerve: Afferent nerve carrying chemoreceptor signals from the carotid body to brainstem respiratory centres.

References

1. Transgenic NADH dehydrogenase restores oxygen regulation of breathing in mitochondrial complex I-deficient mice. Nature Communications (2023).
2. Hif-2α programmes oxygen chemosensitivity in chromaffin cells. Journal of Clinical Investigation (2024).
3. Blood oxygen regulation via P2Y12R expressed in the carotid body. Respiratory Research (2024).
4. The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension. Nature Communications (2013).
5. Sensory Processing and Integration at the Carotid Body Tripartite Synapse: Neurotransmitter Functions and Effects of Chronic Hypoxia. Frontiers in Physiology (2018).
6. Carotid body, insulin, and metabolic diseases: unraveling the links. Frontiers in Physiology (2014).