Bicuculline dialysis in the retrotrapezoid nucleus (RTN) region stimulates breathing in the awake rat

Nattie, Eugene E.; Shi, Jing; Li, Aihua

doi:10.1016/s0034-5687(00)00212-7

Cited by 32 publications

(26 citation statements)

References 28 publications

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“…The choice, by nature, of 40 mm Hg as the normal mammalian value seems linked to acid-base balance and the maintenance of a normal extracellular pH of 7.4 (106, 150, 175, 209, 211). The initial evolutionary appearance of chemoreceptors is suggested to have occurred in ectotherm air breathing vertebrates.…”

Section: The Evolution Of Central Chemoreceptionmentioning

confidence: 99%

Central Chemoreceptors: Locations and Functions

Nattie¹,

Li²

2012

Comprehensive Physiology

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Central chemoreception traditionally refers to a change in ventilation attributable to changes in CO2/H+ detected within the brain. Interest in central chemoreception has grown substantially since the previous Handbook of Physiology published in 1986. Initially, central chemoreception was localized to areas on the ventral medullary surface, a hypothesis complemented by the recent identification of neurons with specific phenotypes near one of these areas as putative chemoreceptor cells. However, there is substantial evidence that many sites participate in central chemoreception some located at a distance from the ventral medulla. Functionally, central chemoreception, via the sensing of brain interstitial fluid H+, serves to detect and integrate information on 1) alveolar ventilation (arterial PCO2), 2) brain blood flow and metabolism and 3) acid-base balance, and, in response, can affect breathing, airway resistance, blood pressure (sympathetic tone) and arousal. In addition, central chemoreception provides a tonic ‘drive’ (source of excitation) at the normal, baseline PCO2 level that maintains a degree of functional connectivity among brainstem respiratory neurons necessary to produce eupneic breathing. Central chemoreception responds to small variations in PCO2 to regulate normal gas exchange and to large changes in PCO2 to minimize acid-base changes. Central chemoreceptor sites vary in function with sex and with development. From an evolutionary perspective, central chemoreception grew out of the demands posed by air vs. water breathing, homeothermy, sleep, optimization of the work of breathing with the ‘ideal’ arterial PCO2, and the maintenance of the appropriate pH at 37°C for optimal protein structure and function.

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Section: The Evolution Of Central Chemoreceptionmentioning

confidence: 99%

Central Chemoreceptors: Locations and Functions

Nattie¹,

Li²

2012

Comprehensive Physiology

Self Cite

204

139

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“…Unlike the above studies, we observed only reduction in tidal volume which leads to changes in minute volume after exposure to hypercapnia. These results are consistent with the possibility that CO2-dependent drive from the RTN primarily regulates tidal volume in unanesthetized animals (Nattie et al, 2001. The suggestion that RTN neurons may control tidal volume was first proposed by Dr. Nattie laboratory in the mid 1990s Nattie, 1995, Li et al, 1999) based on observations that acidification of the RTN with acetazolamide produced changes in tidal volume without modification of the respiratory frequency.…”

Section: Contribution Of Purinergic Signaling Into the Rtn During Hypsupporting

confidence: 84%

O bloqueio purinérgico no núcleo retrotrapezóide (RTN) atenua as respostas respiratórias promovidas pela ativação dos quimiorreflexos central e periférico em ratos.

Barna¹

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Ao Prof. Dr. Thiago dos Santos Moreira que me agraciou com seus ensinamentos, paciência e tempo para que eu me desenvolvesse profissionalmente em seu laboratório e na vida. À Profa. Dra. Ana Carolina T. Takakura pelo apoio e dedicação ao meu projeto.Ao colaborador e surpevisor Prof. Dr. Daniel K. Mulkey o qual me acolheu em seu laboratório e promoveu minha experiência na pesquisa nos Estados Unidos.Aos Prof. Sara Joyce Shammah-Lagnado e Dr. Martin Andreas Metzger e à Ana Maria P. Campos que sempre foram mestres para mim no auxílio da minha formação, me auxiliando em todas minhas dúvidas.Aos meus pais Gilmar e Vanilda, irmão Bernardo, meu marido Julio e sua família que estiveram comigo em todos os momentos, me incentivando a seguir em frente e me apoiando no que fosse preciso, sem os quais eu jamais teria chegado até aqui.À todos os meus amigos, em especial Ana Paula M. Vivas e Luciene A. T. de Souza, e familiares que perceberam minha ausência em muitos momentos importantes mas sempre me incentivaram a seguir em frente.Aos meus grandes amigos do ICB Izabela Martina R. R. de Toledo, Karina Thieme, Talita M. Silva e Luiz Marcelo Oliveira dos quais me orgulho e me espelho e que estiveram comigo em todos os momentos me animando e dividindo suas experiências.Aos meus colegas do ICB pelas experiências divididas no laboratório, durante as disciplinas e em especial aos cursos de verão, os quais me deram a chance de colocar a prova meus conhecimentos e ter a maravilhosa experiência da docência. A respiração é um processo neural essencial para a homeostasia do organismo humano, o qual regula os níveis de O 2 e CO 2 no sangue. Evidências sugerem que o ATP mediando a sinalização purinérgica no bulbo ventrolateral rostral (RVLM) contribui para o controle quimiorrreceptor central e periférico regulando a pressão arterial e a respiração. Dessa maneira, neurônios do núcleo retrotrapezóide (RTN) agem como quimiorreceptores centrais que em parte respondem ao ATP liberado pelo aumento de CO 2 por meio da ativação de receptores P2 ainda desconhecidos, regulando a respiração, e os neurônios catecolaminérgico C1 regulam as respostas de pressão arterial à ativação dos quimiorreceptores periféricos por um mecanismo dependente de receptor P2Y. No entanto, as potenciais contribuições da sinalização purinérgica, no RTN, na função cardiorrespiratória em animais não anestesiados ainda não foram testadas. Neste estudo mostramos que a injeção unilateral de ATP no RTN promoveu aumento da atividade cardiorrespiratória por um mecanismo dependente de receptores P2. Mostramos também que as injeções bilaterais, no RTN, do bloqueador de receptor P2 não específico (PPADS), mas não de receptores específicos P2Y (MRS2179), reduziu a resposta ventilatória à hipercapnia (7% CO 2 ) e hipóxia (8% O 2 ) em ratos não anestesiados. Além disso, a aplicação da adenosina (ADO) no RTN atenuou o aumento da ventilação induzido por hipercapnia in vivo, bem como o disparo dos neurônios in vitro. Estes resultados demonstram que a sinalização mediada por ATP contribui p...

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“…This possibility has been strengthened by a series of in vivo experiments by Nattie and colleagues who showed that chemical activation of the RTN led to increased respiratory drive and the ventilatory response to CO 2 (6,30,43), whereas chemical inhibition of the RTN had the opposite effect (40,44). These studies also found that the contribution of the RTN to respiratory drive is more pronounced in anesthetized animals compared with conscious animals.…”

Section: The Rtn Is An Important Site Of Central Chemoreceptionmentioning

confidence: 99%

“…Several brain regions are thought to participate in chemoreception including the nucleus tractus solitarius, locus coeruleus, medullary raphe, prebotzinger complex, fastigial nucleus of the cerebellum, hypothalamus, and retrotrapezoid nucleus (RTN) (14,22). Although the relative contributions of these putative chemoreceptor regions remains controversial (24, 42), there is compelling evidence that the RTN is an important site of chemoreception (1,6,26,38,43). In this review, we will summarize the properties of chemosensitive RTN neurons; further details on this topic can be found in several recent reviews (23,24,41).…”

mentioning

confidence: 99%

Current ideas on central chemoreception by neurons and glial cells in the retrotrapezoid nucleus

Mulkey

Wenker

Kréneisz

2010

Journal of Applied Physiology

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(23), and recent evidence suggests that RTN chemoreception involves two interrelated mechanisms: H ϩ -mediated activation of pH-sensitive neurons (38) and purinergic signaling (19), possibly from pH-sensitive glial cells. A third, potentially important, aspect of RTN chemoreception is the regulation of blood flow, which is an important determinate of tissue pH and consequently chemoreceptor activity. It is well established in vivo that changes in cerebral blood flow can profoundly affect the chemoreflex (2); e.g., limiting blood flow by vasoconstriction acidifies tissue pH and increases the ventilatory response to CO 2, whereas vasodilation can wash out metabolically produced CO2 from tissue to increase tissue pH and decrease the stimulus at chemoreceptors. In this review, we will summarize the defining characteristics of pH-sensitive neurons and discuss potential contributions of pH-sensitive glial cells as both a source of purinergic drive to pH-sensitive neurons and a modulator of vasculature tone.control of breathing; central chemoreceptor; vascular control; neural-glial interactions CENTRAL CHEMORECEPTION IS the mechanism by which the brain regulates breathing in response to changes in tissue pH, wherein CO 2 /H ϩ chemoreceptors sense pH changes to regulate the depth and frequency of breathing. Several brain regions are thought to participate in chemoreception including the nucleus tractus solitarius, locus coeruleus, medullary raphe, prebotzinger complex, fastigial nucleus of the cerebellum, hypothalamus, and retrotrapezoid nucleus (RTN) (14,22). Although the relative contributions of these putative chemoreceptor regions remains controversial (24, 42), there is compelling evidence that the RTN is an important site of chemoreception (1,6,26,38,43). In this review, we will summarize the properties of chemosensitive RTN neurons; further details on this topic can be found in several recent reviews (23,24,41). Surprisingly, pH-sensitive RTN glial cells, first described by Fukuda et al.(16) more than 30 years ago, have received relatively little attention (9 -11, 46, 53) despite evidence from other brain regions that glial cells can function as important modulators of both neural network activity and vascular tone (25). Therefore, we will also describe general characteristics of glial cells and propose an expanded model of chemoreception that includes a role for RTN glia as a source of excitatory drive to pHsensitive neurons as well as a regulator of local vascular tone. THE RTN IS AN IMPORTANT SITE OF CENTRAL CHEMORECEPTIONThe early work of Mitchell and colleagues more than 40 years ago established that acidification of the ventral medullary surface (area M) stimulates breathing (34); therefore, they concluded that pH-sensitive neurons in this region, later defined as the RTN (57), are able to provide the chemical drive to breathe. This possibility has been strengthened by a series of in vivo experiments by Nattie and colleagues who showed that chemical activation of the RTN led to increased respiratory drive...

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Bicuculline dialysis in the retrotrapezoid nucleus (RTN) region stimulates breathing in the awake rat

Cited by 32 publications

References 28 publications

Central Chemoreceptors: Locations and Functions

Central Chemoreceptors: Locations and Functions

O bloqueio purinérgico no núcleo retrotrapezóide (RTN) atenua as respostas respiratórias promovidas pela ativação dos quimiorreflexos central e periférico em ratos.

Current ideas on central chemoreception by neurons and glial cells in the retrotrapezoid nucleus

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