The Experts below are selected from a list of 1212 Experts worldwide ranked by ideXlab platform
Jose Lopezbarneo - One of the best experts on this subject based on the ideXlab platform.
-
an o2 sensitive Glomus Cell stem Cell synapse induces carotid body growth in chronic hypoxia
Cell, 2014Co-Authors: Aida Plateroluengo, Ricardo Pardal, Susana Gonzalezgranero, Rocio Duran, Blanca Diazcastro, Jose I Piruat, Jose Manuel Garciaverdugo, Jose LopezbarneoAbstract:Summary Neural stem Cells (NSCs) exist in germinal centers of the adult brain and in the carotid body (CB), an oxygen-sensing organ that grows under chronic hypoxemia. How stem Cell lineage differentiation into mature Glomus Cells is coupled with changes in physiological demand is poorly understood. Here, we show that hypoxia does not affect CB NSC proliferation directly. Rather, mature Glomus Cells expressing endothelin-1, the O 2 -sensing elements in the CB that secrete neurotransmitters in response to hypoxia, establish abundant synaptic-like contacts with stem Cells, which express endothelin receptors, and instruct their growth. Inhibition of Glomus Cell transmitter release or their selective destruction markedly diminishes CB Cell growth during hypoxia, showing that CB NSCs are under the direct "synaptic" control of the mature O 2 -sensitive Cells. Thus, Glomus Cells not only acutely activate the respiratory center but also induce NSC-dependent CB hypertrophy necessary for acclimatization to chronic hypoxemia.
-
carotid body chemosensory responses in mice deficient of task channels
The Journal of General Physiology, 2010Co-Authors: Patricia Ortegasaenz, Konstantin L Levitsky, Maria T Marcosalmaraz, Victoria Bonillahenao, Alberto Pascual, Jose LopezbarneoAbstract:Background K+ channels of the TASK family are believed to participate in sensory transduction by chemoreceptor (Glomus) Cells of the carotid body (CB). However, studies on the systemic CB-mediated ventilatory response to hypoxia and hypercapnia in TASK1- and/or TASK3-deficient mice have yielded conflicting results. We have characterized the Glomus Cell phenotype of TASK-null mice and studied the responses of individual Cells to hypoxia and other chemical stimuli. CB morphology and Glomus Cell size were normal in wild-type as well as in TASK1−/− or double TASK1/3−/− mice. Patch-clamped TASK1/3-null Glomus Cells had significantly higher membrane resistance and less hyperpolarized resting potential than their wild-type counterpart. These electrical parameters were practically normal in TASK1−/− Cells. Sensitivity of background currents to changes of extraCellular pH was drastically diminished in TASK1/3-null Cells. In contrast with these observations, responsiveness to hypoxia or hypercapnia of either TASK1−/− or double TASK1/3−/− Cells, as estimated by the amperometric measurement of catecholamine release, was apparently normal. TASK1/3 knockout Cells showed an enhanced secretory rate in basal (normoxic) conditions compatible with their increased excitability. Responsiveness to hypoxia of TASK1/3-null Cells was maintained after pharmacological blockade of maxi-K+ channels. These data in the TASK-null mouse model indicate that TASK3 channels contribute to the background K+ current in Glomus Cells and to their sensitivity to external pH. They also suggest that, although TASK1 channels might be dispensable for O2/CO2 sensing in mouse CB Cells, TASK3 channels (or TASK1/3 heteromers) could mediate hypoxic depolarization of normal Glomus Cells. The ability of TASK1/3−/− Glomus Cells to maintain a powerful response to hypoxia even after blockade of maxi-K+ channels, suggests the existence of multiple sensor and/or effector mechanisms, which could confer upon the Cells a high adaptability to maintain their chemosensory function.
-
carotid body oxygen sensing
European Respiratory Journal, 2008Co-Authors: Jose Lopezbarneo, Ricardo Pardal, Patricia Ortegasaenz, Alberto Pascual, Jose I PiruatAbstract:The carotid body (CB) is a neural crest-derived organ whose major function is to sense changes in arterial oxygen tension to elicit hyperventilation in hypoxia. The CB is composed of clusters of neuron-like Glomus, or type-I, Cells enveloped by glia-like sustentacular, or type-II, Cells. Responsiveness of CB to acute hypoxia relies on the inhibition of O2-sensitive K+ channels in Glomus Cells, which leads to Cell depolarisation, Ca2+ entry and release of transmitters that activate afferent nerve fibres. Although this model of O2 sensing is generally accepted, the molecular mechanisms underlying K+ channel modulation by O2 tension are unknown. Among the putative hypoxia-sensing mechanisms there are: the production of oxygen radicals, either in mitochondria or reduced nicotinamide adenine dinucleotide phosphate oxidases; metabolic mitochondrial inhibition and decrease of intraCellular ATP; disruption of the prolylhydroxylase/hypoxia inducible factor pathway; or decrease of carbon monoxide production by haemoxygenase-2. In chronic hypoxia, the CB grows with increasing Glomus Cell number. The current authors have identified, in the CB, neural stem Cells, which can differentiate into Glomus Cells. Cell fate experiments suggest that the CB progenitors are the glia-like sustentacular Cells. The CB appears to be involved in the pathophysiology of several prevalent human diseases. SERIES “HYPOXIA: ERS LUNG SCIENCE CONFERENCE” Edited by N. Weissmann Number 5 in this Series
-
the mitochondrial sdhd gene is required for early embryogenesis and its partial deficiency results in persistent carotid body Glomus Cell activation with full responsiveness to hypoxia
Molecular and Cellular Biology, 2004Co-Authors: Jose I Piruat, Oscar C Pintado, Patricia Ortegasaenz, Marta Roche, Jose LopezbarneoAbstract:The SDHD gene encodes one of the two membrane-anchoring proteins of the succinate dehydrogenase (complex II) of the mitochondrial electron transport chain. This gene has recently been proposed to be involved in oxygen sensing because mutations that cause loss of its function produce hereditary familiar paraganglioma, a tumor of the carotid body (CB), the main arterial chemoreceptor that senses oxygen levels in the blood. Here, we report the generation of a SDHD knockout mouse, which to our knowledge is the first mammalian model lacking a protein of the electron transport chain. Homozygous SDHD / animals die at early embryonic stages. Heterozygous SDHD / mice show a general, noncompensated deficiency of succinate dehydrogenase activity without alterations in body weight or major physiological dysfunction. The responsiveness to hypoxia of CBs from SDHD / mice remains intact, although the loss of an SDHD allele results in abnormal enhancement of resting CB activity due to a decrease of K conductance and persistent Ca 2 influx into Glomus Cells. This CB overactivity is linked to a subtle Glomus Cell hypertrophy and hyperplasia. These observations indicate that constitutive activation of SDHD / Glomus Cells precedes CB tumor transformation. They also suggest that, contrary to previous beliefs, mitochondrial complex II is not directly involved in CB oxygen sensing.
-
low glucose sensing Cells in the carotid body
Nature Neuroscience, 2002Co-Authors: Ricardo Pardal, Jose LopezbarneoAbstract:Decreased plasma glucose concentration elicits a complex neuroendocrine response that prevents or rapidly corrects hypoglycemia as required to preserve brain function1,2,3,4; however, where and how low glucose is sensed is unknown4,5,6. Here we show that low glucose increases secretion from Glomus Cells in the carotid bodies, sensory organs whose stimulation by hypoxia produces sympathetic activation, by a process that depends on extraCellular Ca2+ influx and is paralleled by inhibition of voltage-gated K+ channels. We propose a new glucose-sensing role for the carotid body Glomus Cell that serves to integrate information about blood glucose and O2 levels and to activate counterregulatory responses.
Yoko Kameda - One of the best experts on this subject based on the ideXlab platform.
-
Hes1 is required for the development of the superior cervical ganglion of sympathetic trunk and the carotid body.
Developmental Dynamics, 2012Co-Authors: Yoko Kameda, Takayoshi Saitoh, Noriko Nemoto, Tokio Katoh, Sachiko IsekiAbstract:Hes1 gene represses the expression of proneural basic helix–loop–helix (bHLH) factor Mash1, which is essential for the differentiation of the sympathetic ganglia and carotid body Glomus Cells. The sympathetic ganglia, carotid body, and common carotid artery in Wnt1-Cre/R26R double transgenic mice were intensely labeled by X-gal staining, i.e., the neural crest origin. The deficiency of Hes1 caused severe hypoplasia of the superior cervical ganglion (SCG). At embryonic day (E) 17.5–E18.5, the volume of the SCG in Hes1 null mutants was reduced to 26.4% of the value in wild-type mice. In 4 of 30 cases (13.3%), the common carotid artery derived from the third arch artery was absent in the null mutants, and the carotid body was not formed. When the common carotid artery was retained, the organ grew in the wall of the third arch artery and Glomus Cell precursors were provided from the SCG in the null mutants as well as in wild-types. However, the volume of carotid body in the null mutants was only 52.5% of the value in wild-types at E17.5–E18.5. These results suggest that Hes1 plays a critical role in regulating the development of neural crest derivatives in the mouse cervical region. Developmental Dynamics 241:1289–1300, 2012. V C 2012 Wiley Periodicals, Inc. Key findings: � Hes1 gene plays a role in maintaining the undifferentiated Cells during development. � Hes1 null mutant embryos displayed a severe hypoplasia of the superior cervical ganglion (SCG) of sympathetic trunk. � Hes1 null mutants failed to form the common carotid artery as a partially penetrated phenotype (13.3%), resulting in the absence of the carotid body. � When the carotid artery was retained, the carotid body of the null mutants was smaller in size than that of wild types. � Neural crest derivatives, including the SCG, carotid body, and common carotid artery, were affected by the lack of Hes1.
-
frs2 alpha 2f 2f mice lack carotid body and exhibit abnormalities of the superior cervical sympathetic ganglion and carotid sinus nerve
Developmental Biology, 2008Co-Authors: Yoko Kameda, Masataka Ito, Toshiyuki Nishimaki, Noriko GotohAbstract:The docking protein FRS2 alpha is an important mediator of fibroblast growth factor (FGF)-induced signal transduction, and functions by linking FGF receptors (FGFRs) to a variety of intraCellular signaling pathways. We show that the carotid body is absent in FRS2 alpha(2F/2F) mice, in which the Shp2-binding sites of FRS2 alpha are disrupted. We also show that the carotid body rudiment is not formed in the wall of the third arch artery in mutant embryos. In wild-type mice, the superior cervical ganglion of the sympathetic trunk connects to the carotid body in the carotid bifurcation region, and extends thick nerve bundles into the carotid body. In FRS2 alpha(2F/2F) mice, the superior cervical ganglion was present in the lower cervical region as an elongated feature, but failed to undergo cranio-ventral migration. In addition, few neuronal processes extended from the ganglion into the carotid bifurcation region. The number of carotid sinus nerve fibers that reached the carotid bifurcation region was markedly decreased, and baroreceptor fibers belonging to the glossopharyngeal nerve were absent from the basal part of the internal carotid artery in FRS2 alpha(2F/2F) mutant mice. In some of the mutant mice (5 out of 14), baroreceptors and some Glomus Cells were distributed in the wall of the common carotid artery, onto which the sympathetic ganglion abutted. We propose that the sympathetic ganglion provides Glomus Cell precursors into the third arch artery derivative in the presence of sensory fibers of the glossopharyngeal nerve.
-
FRS2α2F/2F mice lack carotid body and exhibit abnormalities of the superior cervical sympathetic ganglion and carotid sinus nerve
Developmental biology, 2007Co-Authors: Yoko Kameda, Masataka Ito, Toshiyuki Nishimaki, Noriko GotohAbstract:The docking protein FRS2 alpha is an important mediator of fibroblast growth factor (FGF)-induced signal transduction, and functions by linking FGF receptors (FGFRs) to a variety of intraCellular signaling pathways. We show that the carotid body is absent in FRS2 alpha(2F/2F) mice, in which the Shp2-binding sites of FRS2 alpha are disrupted. We also show that the carotid body rudiment is not formed in the wall of the third arch artery in mutant embryos. In wild-type mice, the superior cervical ganglion of the sympathetic trunk connects to the carotid body in the carotid bifurcation region, and extends thick nerve bundles into the carotid body. In FRS2 alpha(2F/2F) mice, the superior cervical ganglion was present in the lower cervical region as an elongated feature, but failed to undergo cranio-ventral migration. In addition, few neuronal processes extended from the ganglion into the carotid bifurcation region. The number of carotid sinus nerve fibers that reached the carotid bifurcation region was markedly decreased, and baroreceptor fibers belonging to the glossopharyngeal nerve were absent from the basal part of the internal carotid artery in FRS2 alpha(2F/2F) mutant mice. In some of the mutant mice (5 out of 14), baroreceptors and some Glomus Cells were distributed in the wall of the common carotid artery, onto which the sympathetic ganglion abutted. We propose that the sympathetic ganglion provides Glomus Cell precursors into the third arch artery derivative in the presence of sensory fibers of the glossopharyngeal nerve.
-
Mash1 is required for Glomus Cell formation in the mouse carotid body
Developmental Biology, 2005Co-Authors: Yoko KamedaAbstract:Abstract The carotid body consists of chemoreceptive Glomus Cells, sustentacular Cells and nerve endings. The murine carotid body, located at the carotid bifurcation, is always joined to the superior cervical ganglion of the sympathetic trunk. Glomus Cells and sympathetic neurons are immunoreactive for the TuJ1, PGP9.5, tyrosine hydroxylase (TH) and neuropeptide Y (NPY) markers. Glomus Cells are also immunoreactive for serotonin (5-HT). A targeted mutation of Mash1, a mouse homolog of the Drosophila achaete–scute complex, results in the elimination of sympathetic ganglia. In Mash1 null mutant mice, the carotid body primordium forms normally in the wall of the third arch artery at embryonic day (E) 13.0 and continues to develop, although the superior cervical ganglion is completely absent. However, no Cells in the mutant carotid body display the TuJ1, PGP 9.5, TH, NPY and 5-HT markers throughout development. The absence of Glomus Cells was also confirmed by electron microscopy. The carotid body of newborn null mutants is composed of mesenchymal-like Cells and nerve fibers. Many Cells immunoreactive for the S-100 protein, a sustentacular Cell marker, appear in the mutant carotid body during fetal development. The Mash1 gene is thus required for the genesis of Glomus Cells but not for sustentacular Cells.
Marina C. M. Franck - One of the best experts on this subject based on the ideXlab platform.
-
Striking parallels between carotid body Glomus Cell and adrenal chromaffin Cell development.
Developmental Biology, 2018Co-Authors: Dorit Hockman, Elisabeth Sock, Marketa Kaucka, Perrine Barraud, Tomoki Otani, Adam Hunt, Anna C. Hartwig, Dominic Waithe, Igor Adameyko, Marina C. M. FranckAbstract:Abstract Carotid body Glomus Cells mediate essential reflex responses to arterial blood hypoxia. They are dopaminergic and secrete growth factors that support dopaminergic neurons, making the carotid body a potential source of patient-specific Cells for Parkinson's disease therapy. Like adrenal chromaffin Cells, which are also hypoxia-sensitive, Glomus Cells are neural crest-derived and require the transcription factors Ascl1 and Phox2b; otherwise, their development is little understood at the molecular level. Here, analysis in chicken and mouse reveals further striking molecular parallels, though also some differences, between Glomus and adrenal chromaffin Cell development. Moreover, histology has long suggested that Glomus Cell precursors are ‘emigres’ from neighbouring ganglia/nerves, while multipotent nerve-associated glial Cells are now known to make a significant contribution to the adrenal chromaffin Cell population in the mouse. We present conditional genetic lineage-tracing data from mice supporting the hypothesis that progenitors expressing the glial marker proteolipid protein 1, presumably located in adjacent ganglia/nerves, also contribute to Glomus Cells. Finally, we resolve a paradox for the ‘emigre’ hypothesis in the chicken - where the nearest ganglion to the carotid body is the nodose, in which the satellite glia are neural crest-derived, but the neurons are almost entirely placode-derived - by fate-mapping putative nodose neuronal 'emigres' to the neural crest.
-
Striking parallels between carotid body Glomus Cell and adrenal chromaffin Cell development.
Developmental biology, 2018Co-Authors: Dorit Hockman, Elisabeth Sock, Marketa Kaucka, Perrine Barraud, Tomoki Otani, Adam Hunt, Anna C. Hartwig, Dominic Waithe, Igor Adameyko, Marina C. M. FranckAbstract:Carotid body Glomus Cells mediate essential reflex responses to arterial blood hypoxia. They are dopaminergic and secrete growth factors that support dopaminergic neurons, making the carotid body a potential source of patient-specific Cells for Parkinson's disease therapy. Like adrenal chromaffin Cells, which are also hypoxia-sensitive, Glomus Cells are neural crest-derived and require the transcription factors Ascl1 and Phox2b; otherwise, their development is little understood at the molecular level. Here, analysis in chicken and mouse reveals further striking molecular parallels, though also some differences, between Glomus and adrenal chromaffin Cell development. Moreover, histology has long suggested that Glomus Cell precursors are 'émigrés' from neighbouring ganglia/nerves, while multipotent nerve-associated glial Cells are now known to make a significant contribution to the adrenal chromaffin Cell population in the mouse. We present conditional genetic lineage-tracing data from mice supporting the hypothesis that progenitors expressing the glial marker proteolipid protein 1, presumably located in adjacent ganglia/nerves, also contribute to Glomus Cells. Finally, we resolve a paradox for the 'émigré' hypothesis in the chicken - where the nearest ganglion to the carotid body is the nodose, in which the satellite glia are neural crest-derived, but the neurons are almost entirely placode-derived - by fate-mapping putative nodose neuronal 'émigrés' to the neural crest.
Noriko Gotoh - One of the best experts on this subject based on the ideXlab platform.
-
frs2 alpha 2f 2f mice lack carotid body and exhibit abnormalities of the superior cervical sympathetic ganglion and carotid sinus nerve
Developmental Biology, 2008Co-Authors: Yoko Kameda, Masataka Ito, Toshiyuki Nishimaki, Noriko GotohAbstract:The docking protein FRS2 alpha is an important mediator of fibroblast growth factor (FGF)-induced signal transduction, and functions by linking FGF receptors (FGFRs) to a variety of intraCellular signaling pathways. We show that the carotid body is absent in FRS2 alpha(2F/2F) mice, in which the Shp2-binding sites of FRS2 alpha are disrupted. We also show that the carotid body rudiment is not formed in the wall of the third arch artery in mutant embryos. In wild-type mice, the superior cervical ganglion of the sympathetic trunk connects to the carotid body in the carotid bifurcation region, and extends thick nerve bundles into the carotid body. In FRS2 alpha(2F/2F) mice, the superior cervical ganglion was present in the lower cervical region as an elongated feature, but failed to undergo cranio-ventral migration. In addition, few neuronal processes extended from the ganglion into the carotid bifurcation region. The number of carotid sinus nerve fibers that reached the carotid bifurcation region was markedly decreased, and baroreceptor fibers belonging to the glossopharyngeal nerve were absent from the basal part of the internal carotid artery in FRS2 alpha(2F/2F) mutant mice. In some of the mutant mice (5 out of 14), baroreceptors and some Glomus Cells were distributed in the wall of the common carotid artery, onto which the sympathetic ganglion abutted. We propose that the sympathetic ganglion provides Glomus Cell precursors into the third arch artery derivative in the presence of sensory fibers of the glossopharyngeal nerve.
-
FRS2α2F/2F mice lack carotid body and exhibit abnormalities of the superior cervical sympathetic ganglion and carotid sinus nerve
Developmental biology, 2007Co-Authors: Yoko Kameda, Masataka Ito, Toshiyuki Nishimaki, Noriko GotohAbstract:The docking protein FRS2 alpha is an important mediator of fibroblast growth factor (FGF)-induced signal transduction, and functions by linking FGF receptors (FGFRs) to a variety of intraCellular signaling pathways. We show that the carotid body is absent in FRS2 alpha(2F/2F) mice, in which the Shp2-binding sites of FRS2 alpha are disrupted. We also show that the carotid body rudiment is not formed in the wall of the third arch artery in mutant embryos. In wild-type mice, the superior cervical ganglion of the sympathetic trunk connects to the carotid body in the carotid bifurcation region, and extends thick nerve bundles into the carotid body. In FRS2 alpha(2F/2F) mice, the superior cervical ganglion was present in the lower cervical region as an elongated feature, but failed to undergo cranio-ventral migration. In addition, few neuronal processes extended from the ganglion into the carotid bifurcation region. The number of carotid sinus nerve fibers that reached the carotid bifurcation region was markedly decreased, and baroreceptor fibers belonging to the glossopharyngeal nerve were absent from the basal part of the internal carotid artery in FRS2 alpha(2F/2F) mutant mice. In some of the mutant mice (5 out of 14), baroreceptors and some Glomus Cells were distributed in the wall of the common carotid artery, onto which the sympathetic ganglion abutted. We propose that the sympathetic ganglion provides Glomus Cell precursors into the third arch artery derivative in the presence of sensory fibers of the glossopharyngeal nerve.
Jose I Piruat - One of the best experts on this subject based on the ideXlab platform.
-
an o2 sensitive Glomus Cell stem Cell synapse induces carotid body growth in chronic hypoxia
Cell, 2014Co-Authors: Aida Plateroluengo, Ricardo Pardal, Susana Gonzalezgranero, Rocio Duran, Blanca Diazcastro, Jose I Piruat, Jose Manuel Garciaverdugo, Jose LopezbarneoAbstract:Summary Neural stem Cells (NSCs) exist in germinal centers of the adult brain and in the carotid body (CB), an oxygen-sensing organ that grows under chronic hypoxemia. How stem Cell lineage differentiation into mature Glomus Cells is coupled with changes in physiological demand is poorly understood. Here, we show that hypoxia does not affect CB NSC proliferation directly. Rather, mature Glomus Cells expressing endothelin-1, the O 2 -sensing elements in the CB that secrete neurotransmitters in response to hypoxia, establish abundant synaptic-like contacts with stem Cells, which express endothelin receptors, and instruct their growth. Inhibition of Glomus Cell transmitter release or their selective destruction markedly diminishes CB Cell growth during hypoxia, showing that CB NSCs are under the direct "synaptic" control of the mature O 2 -sensitive Cells. Thus, Glomus Cells not only acutely activate the respiratory center but also induce NSC-dependent CB hypertrophy necessary for acclimatization to chronic hypoxemia.
-
carotid body oxygen sensing
European Respiratory Journal, 2008Co-Authors: Jose Lopezbarneo, Ricardo Pardal, Patricia Ortegasaenz, Alberto Pascual, Jose I PiruatAbstract:The carotid body (CB) is a neural crest-derived organ whose major function is to sense changes in arterial oxygen tension to elicit hyperventilation in hypoxia. The CB is composed of clusters of neuron-like Glomus, or type-I, Cells enveloped by glia-like sustentacular, or type-II, Cells. Responsiveness of CB to acute hypoxia relies on the inhibition of O2-sensitive K+ channels in Glomus Cells, which leads to Cell depolarisation, Ca2+ entry and release of transmitters that activate afferent nerve fibres. Although this model of O2 sensing is generally accepted, the molecular mechanisms underlying K+ channel modulation by O2 tension are unknown. Among the putative hypoxia-sensing mechanisms there are: the production of oxygen radicals, either in mitochondria or reduced nicotinamide adenine dinucleotide phosphate oxidases; metabolic mitochondrial inhibition and decrease of intraCellular ATP; disruption of the prolylhydroxylase/hypoxia inducible factor pathway; or decrease of carbon monoxide production by haemoxygenase-2. In chronic hypoxia, the CB grows with increasing Glomus Cell number. The current authors have identified, in the CB, neural stem Cells, which can differentiate into Glomus Cells. Cell fate experiments suggest that the CB progenitors are the glia-like sustentacular Cells. The CB appears to be involved in the pathophysiology of several prevalent human diseases. SERIES “HYPOXIA: ERS LUNG SCIENCE CONFERENCE” Edited by N. Weissmann Number 5 in this Series
-
the mitochondrial sdhd gene is required for early embryogenesis and its partial deficiency results in persistent carotid body Glomus Cell activation with full responsiveness to hypoxia
Molecular and Cellular Biology, 2004Co-Authors: Jose I Piruat, Oscar C Pintado, Patricia Ortegasaenz, Marta Roche, Jose LopezbarneoAbstract:The SDHD gene encodes one of the two membrane-anchoring proteins of the succinate dehydrogenase (complex II) of the mitochondrial electron transport chain. This gene has recently been proposed to be involved in oxygen sensing because mutations that cause loss of its function produce hereditary familiar paraganglioma, a tumor of the carotid body (CB), the main arterial chemoreceptor that senses oxygen levels in the blood. Here, we report the generation of a SDHD knockout mouse, which to our knowledge is the first mammalian model lacking a protein of the electron transport chain. Homozygous SDHD / animals die at early embryonic stages. Heterozygous SDHD / mice show a general, noncompensated deficiency of succinate dehydrogenase activity without alterations in body weight or major physiological dysfunction. The responsiveness to hypoxia of CBs from SDHD / mice remains intact, although the loss of an SDHD allele results in abnormal enhancement of resting CB activity due to a decrease of K conductance and persistent Ca 2 influx into Glomus Cells. This CB overactivity is linked to a subtle Glomus Cell hypertrophy and hyperplasia. These observations indicate that constitutive activation of SDHD / Glomus Cells precedes CB tumor transformation. They also suggest that, contrary to previous beliefs, mitochondrial complex II is not directly involved in CB oxygen sensing.