Kawai Akira, Onimaru Hiroshi, Homma Ikuo
Department of Physiology, Showa University, School of Medicine, Tokyo, Japan.
J Physiol. 2006 Apr 15;572(Pt 2):525-37. doi: 10.1113/jphysiol.2005.102533. Epub 2006 Feb 9.
We investigated mechanisms of CO(2)/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 mm) or by changing pH from 7.8 to 7.2 by reducing HCO(3)(-) 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 membrane 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 burst rate. Pre-inspiratory 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.
我们通过测量新生大鼠脑干脊髓标本中吸气前神经元的膜电位，来研究延髓呼吸中枢中CO₂/H⁺化学感受的机制，这些吸气前神经元被认为是呼吸节律发生器。通过在恒定HCO₃⁻浓度（26 mM）下将灌流液CO₂浓度从2%改变至8%，或在恒定CO₂（5%）下通过降低HCO₃⁻浓度将pH从7.8改变至7.2来测试神经元反应。呼吸性酸中毒和代谢性酸中毒均导致神经元去极化，伴有兴奋性突触输入增加和爆发频率增加。呼吸性酸中毒增强了神经元驱动电位的幅度。在存在河豚毒素（TTX）的情况下，呼吸性酸中毒和代谢性酸中毒期间膜去极化持续存在。然而，去极化程度小于应用TTX之前，这表明一些神经元对CO₂/H⁺具有内在化学敏感性，而另一些则具有突触化学敏感性。应用Ba²⁺可阻断呼吸性酸中毒引起的膜去极化，而应用Cd²⁺和Ba²⁺后，对代谢性酸中毒的显著去极化仍然存在。我们得出结论，呼吸性酸中毒期间对CO₂/H⁺变化的内在反应由钾通道介导，而代谢性酸中毒期间则通过其他一些机制起作用。在低Ca²⁺、高Mg²⁺溶液中，CO₂浓度升高诱导膜去极化，同时爆发频率增加。吸气前神经元可通过整合这些机制来调节其爆发频率，使其基线膜电位适应外部CO₂/H⁺变化。因此，在脑干脊髓标本中，吸气前神经元可能在中枢化学感受调节呼吸节律中发挥重要作用。
