Physiology of the Carotid Body: From Molecules to Disease

2020 ◽  
Vol 82 (1) ◽  
pp. 127-149 ◽  
Author(s):  
Patricia Ortega-Sáenz ◽  
José López-Barneo
Keyword(s):  
Carotid Body ◽  
Molecular Mechanisms ◽  
Carotid Bifurcation ◽  
Sensory Cells ◽  
Glomus Cells ◽  
Cell Niche ◽  
And Function ◽  
Sensory Fibers ◽  
Acute Oxygen Sensing ◽  
Arterial Chemoreceptor

The carotid body (CB) is an arterial chemoreceptor organ located in the carotid bifurcation and has a well-recognized role in cardiorespiratory regulation. The CB contains neurosecretory sensory cells (glomus cells), which release transmitters in response to hypoxia, hypercapnia, and acidemia to activate afferent sensory fibers terminating in the respiratory and autonomic brainstem centers. Knowledge of the physiology of the CB has progressed enormously in recent years. Herein we review advances concerning the organization and function of the cellular elements of the CB, with emphasis on the molecular mechanisms of acute oxygen sensing by glomus cells. We introduce the modern view of the CB as a multimodal integrated metabolic sensor and describe the properties of the CB stem cell niche, which support CB growth during acclimatization to chronic hypoxia. Finally, we discuss the increasing medical relevance of CB dysfunction and its potential impact on the mechanisms of disease.

scholarly journals Neurotransmitter Modulation of Carotid Body Germinal Niche

2020 ◽  
Vol 21 (21) ◽  
pp. 8231
Author(s):  
Verónica Sobrino ◽  
Aida Platero-Luengo ◽  
Valentina Annese ◽  
Elena Navarro-Guerrero ◽  
Patricia González-Rodríguez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Carotid Body ◽  
Close Contact ◽  
Cell Activity ◽  
Cell Types ◽  
Clinical Tool ◽  
Multipotent Stem Cells ◽  
Glomus Cells ◽  
Afferent Fibers ◽  
Sensory Fibers

The carotid body (CB), a neural-crest-derived organ and the main arterial chemoreceptor in mammals, is composed of clusters of cells called glomeruli. Each glomerulus contains neuron-like, O2-sensing glomus cells, which are innervated by sensory fibers of the petrosal ganglion and are located in close contact with a dense network of fenestrated capillaries. In response to hypoxia, glomus cells release transmitters to activate afferent fibers impinging on the respiratory and autonomic centers to induce hyperventilation and sympathetic activation. Glomus cells are embraced by interdigitating processes of sustentacular, glia-like, type II cells. The CB has an extraordinary structural plasticity, unusual for a neural tissue, as it can grow several folds its size in subjects exposed to sustained hypoxia (as for example in high altitude dwellers or in patients with cardiopulmonary diseases). CB growth in hypoxia is mainly due to the generation of new glomeruli and blood vessels. In recent years it has been shown that the adult CB contains a collection of quiescent multipotent stem cells, as well as immature progenitors committed to the neurogenic or the angiogenic lineages. Herein, we review the main properties of the different cell types in the CB germinal niche. We also summarize experimental data suggesting that O2-sensitive glomus cells are the master regulators of CB plasticity. Upon exposure to hypoxia, neurotransmitters and neuromodulators released by glomus cells act as paracrine signals that induce proliferation and differentiation of multipotent stem cells and progenitors, thus causing CB hypertrophy and an increased sensory output. Pharmacological modulation of glomus cell activity might constitute a useful clinical tool to fight pathologies associated with exaggerated sympathetic outflow due to CB overactivation.

scholarly journals Oxygen sensing by the carotid body: mechanisms and role in adaptation to hypoxia

2016 ◽  
Vol 310 (8) ◽  
pp. C629-C642 ◽  
Author(s):  
José López-Barneo ◽  
Patricia González-Rodríguez ◽  
Lin Gao ◽  
M. Carmen Fernández-Agüera ◽  
Ricardo Pardal ◽  
...  
Keyword(s):  
Carotid Body ◽  
Close Contact ◽  
Nerve Fibers ◽  
Whole Body ◽  
Adaptation To Hypoxia ◽  
Glomus Cells ◽  
Adaptive Processes ◽  
Cell Depolarization ◽  
Sensory Fibers

Oxygen (O2) is fundamental for cell and whole-body homeostasis. Our understanding of the adaptive processes that take place in response to a lack of O2 (hypoxia) has progressed significantly in recent years. The carotid body (CB) is the main arterial chemoreceptor that mediates the acute cardiorespiratory reflexes (hyperventilation and sympathetic activation) triggered by hypoxia. The CB is composed of clusters of cells (glomeruli) in close contact with blood vessels and nerve fibers. Glomus cells, the O2-sensitive elements in the CB, are neuron-like cells that contain O2-sensitive K+ channels, which are inhibited by hypoxia. This leads to cell depolarization, Ca2+ entry, and the release of transmitters to activate sensory fibers terminating at the respiratory center. The mechanism whereby O2 modulates K+ channels has remained elusive, although several appealing hypotheses have been postulated. Recent data suggest that mitochondria complex I signaling to membrane K+ channels plays a fundamental role in acute O2 sensing. CB activation during exposure to low Po2 is also necessary for acclimatization to chronic hypoxia. CB growth during sustained hypoxia depends on the activation of a resident population of stem cells, which are also activated by transmitters released from the O2-sensitive glomus cells. These advances should foster further studies on the role of CB dysfunction in the pathogenesis of highly prevalent human diseases.

scholarly journals Acute oxygen sensing by the carotid body: a rattlebag of molecular mechanisms

2017 ◽  
Vol 596 (15) ◽  
pp. 2969-2976 ◽  
Author(s):  
Ryan J. Rakoczy ◽  
Christopher N. Wyatt
Keyword(s):  
Carotid Body ◽  
Molecular Mechanisms ◽  
Oxygen Sensing ◽  
Acute Oxygen Sensing

scholarly journals Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α

2020 ◽  
Vol 11 ◽  
Author(s):  
Patricia Ortega-Sáenz ◽  
Alejandro Moreno-Domínguez ◽  
Lin Gao ◽  
José López-Barneo
Keyword(s):  
Carotid Body ◽  
Molecular Mechanisms ◽  
Experimental Tests ◽  
Mouse Genetics ◽  
Glomus Cells ◽  
Body Activity ◽  
Solid Foundation ◽  
Physical And Chemical ◽  
Membrane Signaling

Carotid body glomus cells are multimodal arterial chemoreceptors able to sense and integrate changes in several physical and chemical parameters in the blood. These cells are also essential for O2 homeostasis. Glomus cells are prototypical peripheral O2 sensors necessary to detect hypoxemia and to elicit rapid compensatory responses (hyperventilation and sympathetic activation). The mechanisms underlying acute O2 sensing by glomus cells have been elusive. Using a combination of mouse genetics and single-cell optical and electrophysiological techniques, it has recently been shown that activation of glomus cells by hypoxia relies on the generation of mitochondrial signals (NADH and reactive oxygen species), which modulate membrane ion channels to induce depolarization, Ca2+ influx, and transmitter release. The special sensitivity of glomus cell mitochondria to changes in O2 tension is due to Hif2α-dependent expression of several atypical mitochondrial subunits, which are responsible for an accelerated oxidative metabolism and the strict dependence of mitochondrial complex IV activity on O2 availability. A mitochondrial-to-membrane signaling model of acute O2 sensing has been proposed, which explains existing data and provides a solid foundation for future experimental tests. This model has also unraveled new molecular targets for pharmacological modulation of carotid body activity potentially relevant in the treatment of highly prevalent medical conditions.

scholarly journals HIF-2α is essential for carotid body development and function

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
David Macias ◽  
Andrew S Cowburn ◽  
Hortensia Torres-Torrelo ◽  
Patricia Ortega-Sáenz ◽  
José López-Barneo ◽  
...  
Keyword(s):  
Carotid Body ◽  
Transcriptional Responses ◽  
Growth And Survival ◽  
Glomus Cells ◽  
Ventilatory Responses ◽  
Body Development ◽  
Physiological Adaptations ◽  
Oxygen Sensitive ◽  
And Function ◽  
Mtorc1 Activation

Mammalian adaptation to oxygen flux occurs at many levels, from shifts in cellular metabolism to physiological adaptations facilitated by the sympathetic nervous system and carotid body (CB). Interactions between differing forms of adaptive response to hypoxia, including transcriptional responses orchestrated by the Hypoxia Inducible transcription Factors (HIFs), are complex and clearly synergistic. We show here that there is an absolute developmental requirement for HIF-2α, one of the HIF isoforms, for growth and survival of oxygen sensitive glomus cells of the carotid body. The loss of these cells renders mice incapable of ventilatory responses to hypoxia, and this has striking effects on processes as diverse as arterial pressure regulation, exercise performance, and glucose homeostasis. We show that the expansion of the glomus cells is correlated with mTORC1 activation, and is functionally inhibited by rapamycin treatment. These findings demonstrate the central role played by HIF-2α in carotid body development, growth and function.

scholarly journals Organoids as tools to investigate the molecular mechanisms of male infertility and its treatments

Reproduction ◽  
2021 ◽  
Vol 161 (5) ◽  
pp. R103-R112
Author(s):  
Marc Kanbar ◽  
Maxime Vermeulen ◽  
Christine Wyns
Keyword(s):  
Self Assembly ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Testicular Tissue ◽  
Innovative Methods ◽  
Potential Applications ◽  
Cell Niche ◽  
And Function ◽  
Conventional Systems

Organoids are 3D structures characterized by cellular spatial organizations and functions close to the native tissue they mimic. Attempts to create organoids originating from several tissues have now been reported, including the testis. Testicular organoids have the potential to improve our knowledge of the mechanisms that regulate testicular morphogenesis, physiology, and pathophysiology. They could especially prove as useful tools to understand the complex mechanisms involved in the regulation of the germ cell niche in infertility cases as they offer the possibility to control and modify the nature of cell types before self-assembly and thereby opening the perspective for developing innovative methods to restore fertility. To date, there are only few studies targeted at testicular organoids’ formation and even less describing the generation of organoids with both testis-specific structure and function. While researchers described interesting applications with regards to testicular tissue morphogenesis and drug toxicity, further research is needed before testicular organoids would eventually lead to the generation of fertilizing spermatozoa. This review will present the conventional systems used to induce in vitro maturation of testicular cells, describe the different approaches that have been used for the development of testicular organoids and discuss the potential applications they could have in the field of male reproductive biology.

scholarly journals HIF-2α is essential for carotid body development and function

2018 ◽  
Author(s):  
David Macías ◽  
Andrew S. Cowburn ◽  
Hortensia Torres-Torrelo ◽  
Patricia Ortega-Sáenz ◽  
José López-Barneo ◽  
...  
Keyword(s):  
Carotid Body ◽  
Transcriptional Responses ◽  
Growth And Survival ◽  
Glomus Cells ◽  
Ventilatory Responses ◽  
Body Development ◽  
Physiological Adaptations ◽  
Oxygen Sensitive ◽  
And Function ◽  
Mtorc1 Activation

SummaryMammalian adaptation to oxygen flux occurs at many levels, from shifts in cellular metabolism to physiological adaptations facilitated by the sympathetic nervous system and carotid body (CB). Interactions between differing forms of adaptive response to hypoxia, including transcriptional responses orchestrated by the Hypoxia Inducible transcription Factors (HIFs), are complex and clearly synergistic. We show here that there is an absolute developmental requirement for HIF-2a, one of the HIF isoforms, for growth and survival of oxygen sensitive glomus cells of the carotid body. The loss of these cells renders mice incapable of ventilatory responses to hypoxia, and this has striking effects on processes as diverse as arterial pressure regulation, exercise performance, and glucose homeostasis. We show that the expansion of the glomus cells is correlated with mTORC1 activation, and is functionally inhibited by rapamycin treatment. These findings demonstrate the central role played by HIF-2a in carotid body development, growth and function.

Fine Structure of Carotid Body: Normal and Anoxic Cats

1967 ◽  
Vol 25 ◽  
pp. 150-151
Author(s):  
Fadhil Al-Lami ◽  
R.G. Murray
Keyword(s):  
Fine Structure ◽  
Adrenal Medulla ◽  
Carotid Body ◽  
Uranyl Acetate ◽  
Lead Citrate ◽  
Glomus Cells ◽  
Sustentacular Cells ◽  
Carotid Bodies

Although the fine structure of the carotid body has been described in several recent reports, uncertainties remain, and the morphological effects of anoxia on the carotid body cells of the cat have never been reported. We have, therefore, studied the fine structure of the carotid body both in normal and severely anoxic cats, and to test the specificity of the effects, have compared them with the effects on adrenal medulla, kidney, and liver of the same animals. Carotid bodies of 50 normal and 15 severely anoxic cats (9% oxygen in nitrogen) were studied. Glutaraldehyde followed by OsO4 fixations, Epon 812 embedding, and uranyl acetate and lead citrate staining, were the technics employed.We have called the two types of glomus cells enclosed and enclosing cells. They correspond to those previously designated as chemoreceptor and sustentacular cells respectively (1). The enclosed cells forming the vast majority, are irregular in shape with many processes and occasional peripheral densities (Fig. 1).

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