Carotid body denervation in dogs: eupnea and the ventilatory response to hyperoxic hypercapnia

Rodman, J. R.; Curran, Aidan K.; Henderson, K. S.; Dempsey, Jerome A.; Smith, Curtis A.

doi:10.1152/jappl.2001.91.1.328

Cited by 80 publications

(80 citation statements)

References 34 publications

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“…Therefore, we investigated the respiratory response upon hypercapnia and hypoxia using whole-body plethysmography on unrestrained male mice. To reduce the contribution of peripheral chemoreceptors to the CO 2 response, hyperoxic hypercapnia was used instead of normoxic hypercapnia (31).…”

Section: Task2-positive Rtn Cells Are Missing In a Mouse Model For Comentioning

confidence: 99%

Task2 potassium channels set central respiratory CO ₂ and O ₂ sensitivity

Gestreau

Heitzmann

Thomas

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

137

140

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Task2 K + channel expression in the central nervous system is surprisingly restricted to a few brainstem nuclei, including the retrotrapezoid (RTN) region. All Task2-positive RTN neurons were lost in mice bearing a Phox2b mutation that causes the human congenital central hypoventilation syndrome. In plethysmography, Task2 −/− mice showed disturbed chemosensory function with hypersensitivity to low CO 2 concentrations, leading to hyperventilation. Task2 probably is needed to stabilize the membrane potential of chemoreceptive cells. In addition, Task2 −/− mice lost the long-term hypoxia-induced respiratory decrease whereas the acute carotid-body-mediated increase was maintained. The lack of anoxia-induced respiratory depression in the isolated brainstemspinal cord preparation suggested a central origin of the phenotype. Task2 activation by reactive oxygen species generated during hypoxia could silence RTN neurons, thus contributing to respiratory depression. These data identify Task2 as a determinant of central O 2 chemoreception and demonstrate that this phenomenon is due to the activity of a small number of neurons located at the ventral medullary surface.breathing | central chemoreceptors | K2P | KCNK5 | ventral medullary surface S pontaneous breathing requires feedback controls in which detection of blood gases and pH is critical. At present, there is good understanding of the brainstem topology of respiratory centers, and functional measurements in vitro and in vivo have revealed the basic principles of the neuronal network required for respiratory rhythmogenesis and pattern generation. This network comprises several groups of respiratory neurons forming columns extending from the caudal ventrolateral medulla to the dorsolateral pons (1, 2). The activity of this network must be stable yet permanently adjusted to variations of O 2 , CO 2 , and pH during diverse physiological conditions, e.g., sleep, exercise, or high altitude (3). The precise physiological processes by which pH, CO 2 , and O 2 changes are sensed and translated into the appropriate respiratory neural output are important mechanisms that are still a matter of debate (4, 5). Changes in arterial CO 2 / pH are detected by peripheral chemoreceptors, mainly carotid bodies, and multiple chemoreceptive areas within the brainstem. Among the central chemoreceptive areas, two have attracted most attention: the raphe nuclei and the retrotrapezoid nucleus (RTN) (6, 7). The carotid bodies are the major sensors for acute O 2 changes. However, for longer periods of hypoxia, respiratory adaptation is substantially mediated by central mechanisms (8). The ventrolateral medullary surface comprising the RTN and the parafacial respiratory group (pFRG) has been proposed to contain intrinsically CO 2 -and O 2 -sensing neurons (9-12). Recently, a mouse model that carries a mutation of the transcription factor Phox2b, which causes congenital central hypoventilation syndrome in humans, was engineered. A specific loss of a population of Phox2b-expressing RTN/pFRG neurons ...

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Section: Task2-positive Rtn Cells Are Missing In a Mouse Model For Comentioning

confidence: 99%

Task2 potassium channels set central respiratory CO ₂ and O ₂ sensitivity

Gestreau

Heitzmann

Thomas

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

137

140

View full text Add to dashboard Cite

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“…3A,B). We also examined the ventilatory increase caused by hypercapnia (8% CO2), which is mediated by CO2/H + -sensitive cells widely distributed within the brainstem and also by carotid body glomus cells (Nattie, 2001), which significantly contribute to this increase [40% in dogs (Rodman et al, 2001)]. We found that the ventilatory response to hypercapnia was markedly lower in Phox2b lacZ/+ than in Phox2b +/+ pups (Fig.…”

Section: Degeneration Of Epibranchial Placode-derived Ganglia and Of mentioning

confidence: 99%

Phox2bcontrols the development of peripheral chemoreceptors and afferent visceral pathways

et al. 2003

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We report that the afferent relays of visceral (cardiovascular, digestive and respiratory) reflexes, differentiate under the control of the paired-like homeobox gene Phox2b: the neural crest-derived carotid body, a chemosensor organ, degenerates in homozygous mutants, as do the three epibranchial placode-derived visceral sensory ganglia (geniculate, petrosal and nodose), while their central target, the nucleus of the solitary tract,which integrates all visceral information, never forms. These data establish Phox2b as an unusual `circuit-specific' transcription factor devoted to the formation of autonomic reflex pathways. We also show that Phox2b heterozygous mutants have an altered response to hypoxia and hypercapnia at birth and a decreased tyrosine hydroxylase expression in the petrosal chemosensory neurons, thus providing mechanistic insight into congenital central hypoventilation syndrome, which is associated with heterozygous mutations in PHOX2B.

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“…The carotid bodies make a significant contribution to CO 2 sensitivity (Rodman et al, 2001), and the hypoxic sensitivity of peripheral chemoreceptors is reduced in the early postnatal period, but rises toward adult levels over the first weeks of life. However, CO 2 sensitivity at the level of the carotid body seems to be stable during development (Fig.…”

Section: Differential Maturation Between Peripheral Versus Central Chmentioning

confidence: 99%

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Putnam

Conrad

Gdovin

et al. 2005

Respiratory Physiology & Neurobiology

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The ventilatory response to CO 2 changes as a function of neonatal development. In rats, a ventilatory response to CO 2 is present in the first 5 days of life, but this ventilatory response to CO 2 wanes and reaches its lowest point around postnatal day 8. Subsequently, the ventilatory response to CO 2 rises towards adult levels. Similar patterns in the ventilatory response to CO 2 are seen in some other species, although some animals do not exhibit all of these phases. Different developmental patterns of the ventilatory response to CO 2 may be related to the state of development of the animal at birth. The triphasic pattern of responsiveness (early decline, a nadir, and subsequent achievement of adult levels of responsiveness) may arise from the development of several processes, including central neural mechanisms, gas exchange, the neuromuscular junction, respiratory muscles and respiratory mechanics. We only discuss central neural mechanisms here, including altered CO 2 sensitivity of neurons among the various sites of central CO 2 chemosensitivity, changes in astrocytic function during development, the maturation of electrical and chemical synaptic mechanisms (both inhibitory and excitatory mechanisms) or changes in the integration of chemosensory information originating from peripheral and multiple central CO 2 chemosensory sites. Among these central processes, the maturation of synaptic mechanisms seems most important and the relative maturation of synaptic processes may also determine how plastic the response to CO 2 is at any particular age.

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Carotid body denervation in dogs: eupnea and the ventilatory response to hyperoxic hypercapnia

Cited by 80 publications

References 34 publications

Task2 potassium channels set central respiratory CO ₂ and O ₂ sensitivity

Task2 potassium channels set central respiratory CO ₂ and O ₂ sensitivity

Phox2bcontrols the development of peripheral chemoreceptors and afferent visceral pathways

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

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Carotid body denervation in dogs: eupnea and the ventilatory response to hyperoxic hypercapnia

Cited by 80 publications

References 34 publications

Task2 potassium channels set central respiratory CO 2 and O 2 sensitivity

Task2 potassium channels set central respiratory CO 2 and O 2 sensitivity

Phox2bcontrols the development of peripheral chemoreceptors and afferent visceral pathways

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

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Product

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Task2 potassium channels set central respiratory CO ₂ and O ₂ sensitivity

Task2 potassium channels set central respiratory CO ₂ and O ₂ sensitivity