High CO2 chemosensitivity versus wide sensing spectrum: a paradoxical problem and its solutions in cultured brainstem neurons.
High CO2 chemosensitivity versus wide sensing spectrum: a paradoxical problem and its solutions in cultured brainstem neurons.
复制标题
高 CO2 化学敏感性与宽传感谱：培养脑干神经元中的矛盾问题及其解决方案。
DOI：
10.1113/jphysiol.2006.115758
复制
发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Jiang,Chun
中科院分区：
文献类型：
--
作者：
Su,Junda;Yang,Liang;Zhang,Xiaoli;Rojas,Asheebo;Shi,Yun;Jiang,Chun
CO2中枢化学感受器在心肺控制中起重要作用。它们对PCO_2在宽范围内具有高度敏感性。这两种传感特性似乎自相矛盾，因为没有已知的pH传感分子可以同时实现这两种特性。在这里，我们表明，培养的神经元网络很可能解决并行和串行过程的灵敏度与频谱问题。在微电极阵列上培养分离的脑干神经元进行研究。在3周的初始培养期后开始记录。一组神经元被升高的CO2剂量依赖性地刺激，线性响应范围为20至70 Torr。一些神经元的放电率增加了高达30%，以响应1 TorrPCO 2的变化，表明培养的脑干神经元网络在很宽的范围内保持高CO2敏感性。抑制Kir通道选择性地抑制对低碳酸血症和轻度高碳酸血症的神经元反应。阻断ASK通道会影响神经元对更严重高碳酸血症的反应。这些与在异源表达系统中测量的这些K+通道的pKa值一致。CO2化学敏感性降低，但没有消除阻断突触前输入的5-羟色胺，P物质或谷氨酸神经元，表明突触前和突触后神经元有助于CO2化学敏感性。因此，这些结果强烈表明，生理PCO 2范围似乎被多种传感分子覆盖，并且高灵敏度可能是通过培养的脑干神经元中突触放大的细胞机制实现的。
CO2central chemoreceptors play an important role in cardiorespiratory control. They are highly sensitive toPCO2in a broad range. These two sensing properties seem paradoxical as none of the known pH‐sensing molecules can achieve both. Here we show that cultured neuronal networks are likely to solve the sensitivityversusspectrum problem with parallel and serial processes. Studies were performed on dissociated brainstem neurons cultured on microelectrode arrays. Recordings started after a 3 week initial period of culture. A group of neurons were dose‐dependently stimulated by elevated CO2with a linear response ranging from 20 to 70 Torr. The firing rate of some neurons increased by up to 30% in response to a 1 TorrPCO2change, indicating that cultured brainstem neuronal networks retain high CO2sensitivity in a broad range. Inhibition of Kir channels selectively suppressed neuronal responses to hypocapnia and mild hypercapnia. Blockade of TASK channels affected neuronal response to more severe hypercapnia. These were consistent with the pKavalues measured for these K+channels in a heterologous expression system. The CO2chemosensitivity was reduced but not eliminated by blockade of presynaptic input from serotonin, substance P or glutamate neurons, indicating that both pre and postsynaptic neurons contribute to the CO2chemosensitivity. These results therefore strongly suggest that the physiologicalPCO2range appears to be covered by multiple sensing molecules, and that the high sensitivity may be achieved by cellular mechanisms via synaptic amplification in cultured brainstem neurons.