CO2/H+ sensing: peripheral and central chemoreception

Lahiri, S.; Forster, R. E.

doi:10.1016/s1357-2725(03)00050-5

Cited by 129 publications

(89 citation statements)

References 87 publications

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“…The exact location of these receptors remain unknown in birds, but because of similarities in the chemical control of respiration between birds and mammals, central chemoreceptors in birds are thought to be in a similar location to those in mammals (Bouverot, 1978). Chemoreceptive neurons are spread among numerous brain stem regions (Nattie, 1999;Lahiri and Forster, 2003;Putnam et al, 2004). The arterial pH recovery observed in our study probably influenced signalling by chemosensitive neurons by altering cerebrospinal fluid (CSF) pH and intracellular pH of the neurons, but the relationship may not be direct as CSF and arterial pH are regulated differently (e.g., Nattie and Edwards, 1981).…”

Section: Central Chemoreceptor Control Of Ventilatory Adjustmentsmentioning

confidence: 99%

Ventilatory roll off during sustained hypercapnia is gender specific in pekin ducks

Dodd

Scott

Milsom

2007

Respiratory Physiology & Neurobiology

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The objective of the present study was to examine the relative roles of peripheral versus central mechanisms in producing ventilatory adjustments in pekin ducks during prolonged (5 h) hypercapnia (5% inspired CO 2 ), and to determine whether these adjustments differed between male and female ducks. After 20 min of CO 2 exposure, intact ducks increased total ventilation (V E ) 2.5-3-fold above control values, due to large increases (∼200%) in tidal volume (V T ) and slightly smaller increases (∼140%) in breathing frequency (f R ). This response was accompanied by respiratory acidosis (pHa fell from ∼7.46 to ∼7.41) and hypercapnia (Pa CO 2 increased from ∼35 to ∼40 Torr). In males,V E fell progressively thereafter due exclusively to a fall in f R , in parallel with a rapid partial recovery of pH (to 7.44) while Pa CO 2 continued to climb (to ∼42 Torr). In females,V E remained elevated during hypercapnia, and no pH recovery occurred. This suggests that a respiratory decline resulting from acid-base compensation (probably due to HCO 3 − mobilization) occurred in males but not in females. Bicarbonate mobilization, and thus pH compensation, may have been reduced in females due to the CaCO 3 requirements of eggshell formation. In males, the acute ventilatory response was reduced slightly by denervation of the carotid bodies or intrapulmonary chemoreceptors, but there was no effect of denervation of either receptor group on the responses to prolonged CO 2 . We conclude that pH compensation triggered by constant or increasing Pa CO 2 , acting at central chemoreceptors, likely mediates the respiratory adjustments seen in male pekin ducks during hypercapnia. Furthermore, we suggest that this ventilatory response be considered a gender-specific hypercapnic ventilatory roll off, in the context of the various time domains of the hypercapnic ventilatory response.

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Section: Central Chemoreceptor Control Of Ventilatory Adjustmentsmentioning

confidence: 99%

Ventilatory roll off during sustained hypercapnia is gender specific in pekin ducks

Dodd

Scott

Milsom

2007

Respiratory Physiology & Neurobiology

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“…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)(10)(11)(12). Recently, a mouse model that carries a mutation of the transcription factor Phox2b, which causes congenital central hypoventilation syndrome in humans, was engineered.…”

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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.

136

138

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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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“…The sensing of CO 2 levels in the brain involves CO 2 /H ϩ chemoreceptors. CO 2 chemoreceptors were also identified in the central and peripheral nervous system and pulmonary vascular tissues (9,10). However, very little is known about what senses the CO 2 levels and how these tissues respond to hypercapnia.…”

mentioning

confidence: 99%

Elevated CO ₂ levels affect development, motility, and fertility and extend life span in Caenorhabditis elegans

Sharabi

Hurwitz

Simon

et al. 2009

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

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Hypercapnia (high CO2 levels) occurs in a number of lung diseases and it is associated with worse outcomes in patients with chronic obstructive lung disease (COPD). However, it is largely unknown how hypercapnia is sensed and responds in nonneuronal cells. Here, we used C. elegans to study the response to nonanesthetic CO 2 levels and show that levels exceeding 9% induce aberrant motility that is accompanied by age-dependent deterioration of body muscle organization, slowed development, reduced fertility and increased life span. These effects occur independently of the IGF-R, dietary restriction, egg laying or mitochondrial-induced aging pathways. Transcriptional profiling analysis shows specific and dynamic changes in gene expression after 1, 6, or 72 h of exposure to 19% CO 2 including increased transcription of several 7-transmembrane domain and innate immunity genes and a reduction in transcription of many of the MSP genes. Together, these results suggest specific physiological and molecular responses to hypercapnia, which appear to be independent of early heat shock and HIF mediated pathways.aging ͉ gene expression ͉ hypercapnia ͉ muscle deterioration ͉ physiology T he internal environment of a living organism self-regulates CO 2 /H ϩ . In mammals the lungs are the organs that dispose of excess CO 2 produced in the different tissues by adjusting the ventilatory pattern. Hypercapnia occurs in a number of lung disease states and usually reflects hypoventilation inadequate gas exchange. Some investigators have proposed that high CO 2 levels had beneficial effects in models of acute lung injury and proposed the term ''permissive hypercapnia'' and even ''therapeutic hypercapnia'' (1, 2). However, more recent studies have suggested that high pCO 2 can cause oxidative stress in the lung, and injury (3). More recently it has been reported that in rat lungs and human epithelial cells, high pCO 2 decreased alveolar fluid clearance independently of pH and ROS (4, 5). In some reports it has been shown that CO 2 uptake involves the aquaporin and RH1 channels (6, 7). In red blood cells, the RH1 complex also functions as an ammonium transporter (8). The sensing of CO 2 levels in the brain involves CO 2 /H ϩ chemoreceptors. CO 2 chemoreceptors were also identified in the central and peripheral nervous system and pulmonary vascular tissues (9, 10). However, very little is known about what senses the CO 2 levels and how these tissues respond to hypercapnia. The effect of low pH (acidosis) in kidney and lung cells can be altogether separated from that of high CO 2 /HCO 3 Ϫ (4, 11). The genetically tractable model organism, C. elegans, is a very powerful system in which to investigate cellular sensing and response to CO 2 . Despite being an invertebrate, C. elegans has differentiated tissues including hypodermis, epidermis, muscle, nervous system and others. Also demonstrated is the importance of evolutionary conserved genes in studying diseases and specific biological processes including hypoxia, longevity, and others.Recent ...

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CO2/H+ sensing: peripheral and central chemoreception

Cited by 129 publications

References 87 publications

Ventilatory roll off during sustained hypercapnia is gender specific in pekin ducks

Ventilatory roll off during sustained hypercapnia is gender specific in pekin ducks

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

Elevated CO ₂ levels affect development, motility, and fertility and extend life span in Caenorhabditis elegans

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CO2/H+ sensing: peripheral and central chemoreception

Cited by 129 publications

References 87 publications

Ventilatory roll off during sustained hypercapnia is gender specific in pekin ducks

Ventilatory roll off during sustained hypercapnia is gender specific in pekin ducks

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

Elevated CO 2 levels affect development, motility, and fertility and extend life span in Caenorhabditis elegans

Contact Info

Product

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

Elevated CO ₂ levels affect development, motility, and fertility and extend life span in Caenorhabditis elegans