Localization of chemosensitive structures in the isolated brainstem of adult guinea‐pig.

Morin-Surun, Marie-Pierre; Boudinot, Eliane; Schäfer, Thorsten; Denavit-Saubié, Monique

doi:10.1113/jphysiol.1995.sp020724

Cited by 21 publications

(14 citation statements)

References 42 publications

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“…A hypercapnic response, manifest as increased frequency of lung ventilation, is well established for air-breathing lower vertebrates: turtles (17), toads (2, 32), lungfish (29), and gar (42). CO 2 -pH sensitivity of isolated brain stems has been shown for mammals (25,39) and turtles (18) as well as bullfrog tadpoles (37) and adult frogs (20). Reported here is further evidence that the isolated bullfrog brain stem is capable of generating a fictive hypercapnic response in all stages of metamorphosis, and this response is predictable and reliable throughout development.…”

Section: Discussionmentioning

confidence: 60%

Central CO₂chemoreception in developing bullfrogs: anomalous response to acetazolamide

Taylor¹,

Harris²,

Coates

et al. 2003

Journal of Applied Physiology

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Central CO(2) chemoreception and the role of carbonic anhydrase were assessed in brain stems from Rana catesbeiana tadpoles and frogs. Buccal and lung rhythms were recorded from cranial nerve VII and spinal nerve II during normocapnia and hypercapnia before and after treatment with 25 microM acetazolamide. The lung response to acetazolamide mimicked the hypercapnic response in early-stage and midstage metamorphic tadpoles and frogs. In late-stage tadpoles, acetazolamide actually inhibited hypercapnic responses. Acetazolamide and hypercapnia decreased the buccal frequency but had no effect on the buccal duty cycle. Carbonic anhydrase activity was present in the brain stem in every developmental stage. Thus more frequent lung ventilation and concomitantly less frequent buccal ventilation comprised the hypercapnic response, but the response to acetazolamide was not consistent during metamorphosis. Therefore, acetazolamide is not a useful tool for central CO(2) chemoreceptor studies in this species. The reversal of the effect of acetazolamide in late-stage metamorphosis may reflect reorganization of central chemosensory processes during the final transition from aquatic to aerial respiration.

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Section: Discussionmentioning

confidence: 60%

Central CO₂chemoreception in developing bullfrogs: anomalous response to acetazolamide

Taylor¹,

Harris²,

Coates

et al. 2003

Journal of Applied Physiology

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“…When the superfusate was made acid by decreasing solution HCO 3 Ϫ content at constant PCO 2 (metabolic acidosis), burst frequency increased, indicating that these superficial chemosensitive neurons respond differently to acidosis induced by increased CO 2 level compared with metabolic acidosis. Denavit-Saubié et al (92) and Morin-Surun et al (234) further showed that when the perfusate was made hypercapnic, thus activating deeper chemosensitive neurons, there was an increase in burst frequency but a decrease in amplitude. The finding that deeper chemosensitive neurons give a different response to hypercapnia than superficial neurons suggests that there are differences in the response of chemosensitive neurons from different regions to the same stimulus.…”

Section: Reduced Preparationsmentioning

confidence: 92%

“…In the first, the brain stem only was removed from an adult guinea pig (92,234). In this preparation, ventilatory output was measured with suction electrodes on the hypoglossal roots (also reflective of respiration).…”

Section: Reduced Preparationsmentioning

confidence: 99%

Cellular mechanisms involved in CO₂ and acid signaling in chemosensitive neurons

Putnam

Filosa

Ritucci

2004

American Journal of Physiology-Cell Physiology

277

343

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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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“…Whereas superfusion with acid solutions at constant PCO 2 generally led to increases in respiratory (phrenic or hypoglossal) motor drive (9,11,35), isohydric hypercapnia was effective in only some preparations (11,35), or completely failed to drive respiratory motor output (9).…”

Section: Intracellular [H ϩ ] As the Adequate Stimulus To Central Chementioning

confidence: 95%

A Novel Inhibitor of the Na⁺/ H⁺ Exchanger Type 3 Activates the Central Respiratory CO₂ Response and Lowers the Apneic Threshold

Kiwull-Schöne

Wiemann²,

Frede³

et al. 2001

Am J Respir Crit Care Med

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Cultured CO2-sensitive neurons from the ventrolateral medulla of newborn rats enhanced their bioelectric activity upon intracellular acidification induced by inhibition of the Na+/H+ exchanger type 3 (NHE3). Now we detected NHE3 also in the medulla oblongata of adult rabbits. Therefore, this animal model was employed to determine whether NHE3 inhibition also affects central respiratory chemosensitivity in vivo. Seven anesthetized (pentobarbital), vagotomized, paralyzed rabbits were artificially ventilated with O2-enriched air. From the phrenic nerve compound discharge, integrated burst amplitude (IPNA), respiratory rate (fR), and phrenic minute activity (IPNA. fR) were taken as measures of central respiratory rhythm and drive. Effects of potent NHE3 inhibition with the novel brain permeant substance S8218 were studied by comparing respiratory characteristics before and after up to 9.2 +/- 1.1 mg/kg cumulative drug application, yielding average plasma concentrations of 0.9 +/- 0.2 microg/ml. In response to S8218, the baseline level of IPNA. fR was significantly enhanced by an average of 51.0 +/- 6.4% (n = 27, p < 0.0001). The influence of NHE3 inhibition on the respiratory CO2 response was studied at plasma concentrations of S8218 maintained in the range of 0.3 microg/ml (10(-6) M). Although the metabolic acid-base status thereby remained widely unchanged, the group mean apneic threshold PaCO2 was significantly lowered by 0.45 +/- 0.11 kPa (n = 7, p < 0.01), whereby in four of seven animals even strong hyperventilation failed to suppress phrenic nerve rhythmicity completely. Likewise, S8218 significantly augmented IPNA. fR, in the range of PaCO2 between 1 and 6 kPa above threshold, by an average of 38.0 +/- 8.5% (n = 35, p < 0.0001). These in vivo results are compatible with the effects of NHE3 inhibition on chemosensitive brainstem neurons in vitro. Moreover, rhythmogenesis is supported through NHE3 inhibition by lowering the threshold PCO2 for central apnea.

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Localization of chemosensitive structures in the isolated brainstem of adult guinea‐pig.

Cited by 21 publications

References 42 publications

Central CO₂chemoreception in developing bullfrogs: anomalous response to acetazolamide

Central CO₂chemoreception in developing bullfrogs: anomalous response to acetazolamide

Cellular mechanisms involved in CO₂ and acid signaling in chemosensitive neurons

A Novel Inhibitor of the Na⁺/ H⁺ Exchanger Type 3 Activates the Central Respiratory CO₂ Response and Lowers the Apneic Threshold

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Localization of chemosensitive structures in the isolated brainstem of adult guinea‐pig.

Cited by 21 publications

References 42 publications

Central CO2chemoreception in developing bullfrogs: anomalous response to acetazolamide

Central CO2chemoreception in developing bullfrogs: anomalous response to acetazolamide

Cellular mechanisms involved in CO2 and acid signaling in chemosensitive neurons

A Novel Inhibitor of the Na+/ H+ Exchanger Type 3 Activates the Central Respiratory CO2 Response and Lowers the Apneic Threshold

Contact Info

Product

Resources

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Central CO₂chemoreception in developing bullfrogs: anomalous response to acetazolamide

Central CO₂chemoreception in developing bullfrogs: anomalous response to acetazolamide

Cellular mechanisms involved in CO₂ and acid signaling in chemosensitive neurons

A Novel Inhibitor of the Na⁺/ H⁺ Exchanger Type 3 Activates the Central Respiratory CO₂ Response and Lowers the Apneic Threshold