Mechanisms of CO_2/H~+ chemoreception by respiratory rhythm generator neurons in the medulla from newborn rats in vitro

摘要

We investigated mechanisms of CO2/H~+ chemoreception in the respiratory centre of the medulla by measuring membrane potentials of pre-inspiratory neurons, which are putative respiratory rhythm generators, in the brainstem-spinal cord preparation of the neonatal rat. Neuronal response was tested by changing superfusate CO_2 concentration from 2% to 8% at constant HCO_3~(-)~ concentration (26 HIM) or by changing pH from 7.8 to 7.2 by reducing HCO3" concentration at constant CO_2 (5%). Both respiratory and metabolic acidosis lead to depolarization of neurons with increased excitatory synaptic input and increased burst rate. Respiratory acidosis potentiated the amplitude of the neuronal drive potential. In the presence of tetrodotoxin (TTX), membrane depolarization persisted during respiratory and metabolic acidosis. However, the depolarization was smaller than that before application of TTX, which suggests that some neurons are intrinsically, and others synaptically, chemosensitive to CO_2/H~+. Application of Ba~2+ blocked membr ane depolarization by respiratory acidosis, whereas significant depolarization in response to metabolic acidosis still remained after application of Cd~2+ and Ba~2+. We concluded that the intrinsic responses to CO_2/H~+ changes were mediated by potassium channels during respiratory acidosis, and that some other mechanisms operate during metabolic acidosis. In low-Ca~2+, high-Mg~2+ solution, an increased CO_2 concentration induced a membrane depolarization with a simultaneous increase of the bur st rate. Pre-inspir atory neurons could adapt their baseline membrane potential to external CO_2/H~+ changes by integration of these mechanisms to modulate their burst rates. Thus, pre-inspiratory neurons might play an important role in modulation of respiratory rhythm by central chemoreception in the brainstem-spinal cord preparation.