RESUMEN
Breathing is regulated by a host of arousal and sleep-wake state-dependent neuromodulators to maintain respiratory homeostasis. Modulators such as acetylcholine, norepinephrine, histamine, serotonin (5-HT), adenosine triphosphate (ATP), substance P, somatostatin, bombesin, orexin, and leptin can serve complementary or off-setting functions depending on the target cell type and signaling mechanisms engaged. Abnormalities in any of these modulatory mechanisms can destabilize breathing, suggesting that modulatory mechanisms are not overly redundant but rather work in concert to maintain stable respiratory output. The present review focuses on the modulation of a specific cluster of neurons located in the ventral medullary surface, named retrotrapezoid nucleus, that are activated by changes in tissue CO2/H+ and regulate several aspects of breathing, including inspiration and active expiration.
Asunto(s)
Células Quimiorreceptoras/fisiología , Bulbo Raquídeo/fisiología , Receptores de Neurotransmisores/fisiología , Mecánica Respiratoria/fisiología , Adenosina Trifosfato/fisiología , Animales , Neuronas Colinérgicas/fisiología , Humanos , Bulbo Raquídeo/citología , Receptores Purinérgicos/fisiología , Respiración , Neuronas Serotoninérgicas/fisiologíaRESUMEN
Hyperoxia, a model of oxidative stress, can disrupt brain stem function, presumably by an increase in O2 free radicals. Breathing hyperbaric oxygen (HBO2) initially causes hyperoxic hyperventilation, whereas extended exposure to HBO2 disrupts cardiorespiratory control. Presently, it is unknown how hyperoxia affects brain stem neurons. We have tested the hypothesis that hyperoxia increases excitability of neurons of the solitary complex neurons, which is an important region for cardiorespiratory control and central CO2/H+ chemoreception. Intracellular recordings were made in rat medullary slices during exposure to 2-3 atm of HBO2, HBO2 plus antioxidant (Trolox C), and chemical oxidants (N-chlorosuccinimide, chloramine-T). HBO2 increased input resistance and stimulated firing rate in 38% of neurons; both effects of HBO2 were blocked by antioxidant and mimicked by chemical oxidants. Hypercapnia stimulated 32 of 60 (53%) neurons. Remarkably, these CO2/H+-chemosensitive neurons were preferentially sensitive to HBO2; 90% of neurons sensitive to HBO2 and/or chemical oxidants were also CO2/H+ chemosensitive. Conversely, only 19% of HBO2-insensitive neurons were CO2/H+ chemosensitive. We conclude that hyperoxia decreases membrane conductance and stimulates firing of putative central CO2/H+-chemoreceptor neurons by an O2 free radical mechanism. These findings may explain why hyperoxia, paradoxically, stimulates ventilation.
Asunto(s)
Tronco Encefálico/efectos de los fármacos , Dióxido de Carbono/fisiología , Oxigenoterapia Hiperbárica , Neuronas/efectos de los fármacos , Oxidantes/farmacología , Acidosis/metabolismo , Animales , Antioxidantes/farmacología , Análisis de los Gases de la Sangre , Tronco Encefálico/citología , Membrana Celular/efectos de los fármacos , Células Quimiorreceptoras/fisiología , Electrofisiología , Radicales Libres/farmacología , Helio/farmacología , Concentración de Iones de Hidrógeno , Hipercapnia/fisiopatología , Hiperoxia/fisiopatología , Técnicas In Vitro , Modelos Neurológicos , Oxidación-Reducción , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-Dawley , Núcleo Solitario/fisiología , Estimulación QuímicaRESUMEN
Neuronal sensitivity to pressure, barosensitivity, is illustrated by high-pressure nervous syndrome, which manifests as increased central nervous system excitability when heliox or trimix is breathed at >15 atmospheres absolute (ATA). We have tested the hypothesis that smaller levels of pressure (Asunto(s)
Presión Atmosférica
, Síndrome Neurológico de Alta Presión/fisiopatología
, Potenciales de la Membrana/fisiología
, Neuronas/fisiología
, Núcleo Solitario/fisiología
, Acidosis/fisiopatología
, Animales
, Antioxidantes/farmacología
, Calcio/farmacología
, Electrofisiología
, Radicales Libres
, Oxigenoterapia Hiperbárica
, Hipercapnia/fisiopatología
, Técnicas In Vitro
, Magnesio/farmacología
, Potenciales de la Membrana/efectos de los fármacos
, Microelectrodos
, Neuronas/efectos de los fármacos
, Ratas
, Núcleo Solitario/citología
, Núcleo Solitario/efectos de los fármacos
, Sinapsis/efectos de los fármacos
, Sinapsis/fisiología
, Transmisión Sináptica/efectos de los fármacos
, Transmisión Sináptica/fisiología