ATP as a mediator of mammalian central CO<sub>2</sub>chemoreception

Thomas, T; Spyer, K. M.

doi:10.1111/j.1469-7793.2000.00441.x

Cited by 73 publications

(73 citation statements)

References 22 publications

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“…This ATP released in response to chemosensory stimulation would be sufficient to reach respiratory neurons within the VRC and trigger adaptive changes in ventilation. Indeed, the stimulatory effects of ATP on the activity of the rhythm-generating circuits and individual VRC neurons have been demonstrated in several studies from our laboratory and others (Thomas & Spyer 2000;Gourine et al 2003;Lorier et al 2007). It is also plausible that ATP may play a role at other central chemosensory sites as all of them are equipped with an array of different ATP receptors (Yao et al 2000).…”

Section: Central Chemosensitivitymentioning

confidence: 81%

Chemosensory pathways in the brainstem controlling cardiorespiratory activity

Spyer

Gourine

2009

Phil. Trans. R. Soc. B

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Cardiorespiratory activity is controlled by a network of neurons located within the lower brainstem. The basic rhythm of breathing is generated by neuronal circuits within the medullary pre-Bö tzinger complex, modulated by pontine and other inputs from cell groups within the medulla oblongata and then transmitted to bulbospinal pre-motor neurons that relay the respiratory pattern to cranial and spinal motor neurons controlling respiratory muscles. Cardiovascular sympathetic and vagal activities have characteristic discharges that are patterned by respiratory activity. This patterning ensures ventilation-perfusion matching for optimal respiratory gas exchange within the lungs. Peripheral arterial chemoreceptors and central respiratory chemoreceptors are crucial for the maintenance of cardiorespiratory homeostasis. Inputs from these receptors ensure adaptive changes in the respiratory and cardiovascular motor outputs in various environmental and physiological conditions. Many of the connections in the reflex pathway that mediates the peripheral arterial chemoreceptor input have been established. The nucleus tractus solitarii, the ventral respiratory network, presympathetic circuitry and vagal pre-ganglionic neurons at the level of the medulla oblongata are integral components, although supramedullary structures also play a role in patterning autonomic outflows according to behavioural requirements. These medullary structures mediate cardiorespiratory reflexes that are initiated by the carotid and aortic bodies in response to acute changes in PO 2 , PCO 2 and pH in the arterial blood. The level of arterial PCO 2 is the primary factor in determining respiratory drive and although there is a significant role of the arterial chemoreceptors, the principal sensor is located either at or in close proximity to the ventral surface of the medulla. The cellular and molecular mechanisms of central chemosensitivity as well as the neural basis for the integration of central and peripheral chemosensory inputs within the medulla remain challenging issues, but ones that have some emerging answers.

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Section: Central Chemosensitivitymentioning

confidence: 81%

Chemosensory pathways in the brainstem controlling cardiorespiratory activity

Spyer

Gourine

2009

Phil. Trans. R. Soc. B

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“…Another way in which glial cells can modulate neuronal function is by metabolic coupling, largely through the exchange of lactate (89). Finally, glial cells can inhibit neuronal excitability by the release of ATP (251), which is of particular interest because purinoceptors have been implicated in chemosensitive signaling (336,356,357). Thus there are numerous ways in which glial cells can play a role in chemosensitive signaling.…”

Section: Other Factors In Central Chemosensitive Signalingmentioning

confidence: 98%

Cellular mechanisms involved in CO₂ and acid signaling in chemosensitive neurons

Putnam

Filosa

Ritucci

2004

American Journal of Physiology-Cell Physiology

278

344

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An increase in CO(2)/H(+) is a major stimulus for increased ventilation and is sensed by specialized brain stem neurons called central chemosensitive neurons. These neurons appear to be spread among numerous brain stem regions, and neurons from different regions have different levels of chemosensitivity. Early studies implicated changes of pH as playing a role in chemosensitive signaling, most likely by inhibiting a K(+) channel, depolarizing chemosensitive neurons, and thereby increasing their firing rate. Considerable progress has been made over the past decade in understanding the cellular mechanisms of chemosensitive signaling using reduced preparations. Recent evidence has pointed to an important role of changes of intracellular pH in the response of central chemosensitive neurons to increased CO(2)/H(+) levels. The signaling mechanisms for chemosensitivity may also involve changes of extracellular pH, intracellular Ca(2+), gap junctions, oxidative stress, glial cells, bicarbonate, CO(2), and neurotransmitters. The normal target for these signals is generally believed to be a K(+) channel, although it is likely that many K(+) channels as well as Ca(2+) channels are involved as targets of chemosensitive signals. The results of studies of cellular signaling in central chemosensitive neurons are compared with results in other CO(2)- and/or H(+)-sensitive cells, including peripheral chemoreceptors (carotid body glomus cells), invertebrate central chemoreceptors, avian intrapulmonary chemoreceptors, acid-sensitive taste receptor cells on the tongue, and pain-sensitive nociceptors. A multiple factors model is proposed for central chemosensitive neurons in which multiple signals that affect multiple ion channel targets result in the final neuronal response to changes in CO(2)/H(+).

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“…Low to moderate concentrations of CO 2 (ranging from 5% to 35%) cause changes in respiration rate (Thomas & Spyer 2000), heart rate and blood pressure (Dripps & Comroe 1947, Kety & Schmidt 1947, Smith & Harrap 1997, as well as HPA axis activity (Barbaccia et al 1996). High concentrations of CO 2 initially cause similar responses and may induce hyperventilation before respiratory and cardiac depression and subsequent failure (Martoft et al 2003).…”

Section: Physiological Effects/actions Of Comentioning

confidence: 99%

Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats

et al. 2005

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SummaryCarbon dioxide (CO 2 ) is the most commonly used agent for euthanasia of laboratory rodents, used on an estimated tens of millions of laboratory rodents per year worldwide, yet there is a growing body of evidence indicating that exposure to CO 2 causes more than momentary pain and distress in these and other animals. We reviewed the available literature on the use of CO 2 for euthanasia (as well as anaesthesia) and also informally canvassed laboratory animal personnel for their opinions regarding this topic. Our review addresses key issues such as CO 2 flow rate and final concentration, presence of oxygen, and prefilled chambers (the animal is added to the chamber once a predetermined concentration and flow rate have been reached) versus gradual induction (the animal is put into an empty chamber and the gas agent(s) is gradually introduced at a fixed rate). Internationally, animal research standards specify that any procedure that would cause pain or distress in humans should be assumed to do so in non-human animals as well (Public Health Service 1986, US Department of Agriculture 1997, Organization for Economic Cooperation and Development 2000). European Union guidelines, however, specify a certain threshold of pain or distress, such as 'skilled insertion of a hypodermic needle', as the starting point at which regulation of the use of animals in experimental or other scientific procedures begins (Biotechnology Regulatory Atlas n.d.). There is clear evidence in the human literature that CO 2 exposure is painful and distressful, while the non-human literature is equivocal. However, the fact that a number of studies do conclude that CO 2 causes pain and distress in animals indicates a need for careful reconsideration of its use. Finally, this review offers recommendations for alternatives to the use of CO 2 as a euthanasia agent.Keywords Carbon dioxide; euthanasia; pain; distress; anaesthesia; welfare; rodents Carbon dioxide (CO 2 ) is commonly used for euthanasia and anaesthesia of laboratory rodents, largely because of its ease of use, relative safety, and low cost, as well as its capacity to euthanize large numbers of animals in a short time span (Ambrose et al. 2000). In large institutions and those with significant rodent-breeding programmes, large numbers of rodents are often euthanized in a short time (Kline et al. 1963) and an appropriate gas agent is often the best way to approach such a challenge. However, CO 2 is not physiologically inert and the published evidence on whether or not CO 2 administration causes pain or distress in animals raises questions about its routine use. This paper reviews this published evidence and includes information on the effects of CO 2 in both humans and nonhumans. Methodological details are included when possible in order to provide a clear

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ATP as a mediator of mammalian central CO₂chemoreception

Cited by 73 publications

References 22 publications

Chemosensory pathways in the brainstem controlling cardiorespiratory activity

Chemosensory pathways in the brainstem controlling cardiorespiratory activity

Cellular mechanisms involved in CO₂ and acid signaling in chemosensitive neurons

Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats

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ATP as a mediator of mammalian central CO2chemoreception

Cited by 73 publications

References 22 publications

Chemosensory pathways in the brainstem controlling cardiorespiratory activity

Chemosensory pathways in the brainstem controlling cardiorespiratory activity

Cellular mechanisms involved in CO2 and acid signaling in chemosensitive neurons

Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats

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Product

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ATP as a mediator of mammalian central CO₂chemoreception

Cellular mechanisms involved in CO₂ and acid signaling in chemosensitive neurons