Hyperbaric oxygen and chemical oxidants stimulate CO2/H+-sensitive neurons in rat brain stem slices
Hyperbaric oxygen and chemical oxidants stimulate CO2/H+-sensitive neurons in rat brain stem slices
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DOI：
10.1152/japplphysiol.00864.2002
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发表时间：
2003-09-01
影响因子：
3.3
通讯作者：
Dean, JB
中科院分区：
文献类型：
--
作者：
Mulkey, DK;Henderson, RA;Dean, JB
高氧是氧化应激的一种模式，可以破坏脑干功能，可能是由于O-2自由基的增加。呼吸高压氧（HBO2）最初会导致高氧过度通气，而长期暴露于HBO2会破坏心肺控制。目前，高氧如何影响脑干神经元尚不清楚。我们已经验证了高氧增加孤立复杂神经元神经元的兴奋性的假设，这是一个重要的区域，心肺控制和中央CO2/H+化学接受。在暴露于2-3 atm HBO2、HBO2 +抗氧化剂（Trolox C）和化学氧化剂（n -氯琥珀酰亚胺、氯胺- t）时，对大鼠髓质切片进行细胞内记录。HBO2增加了38%神经元的输入电阻和刺激放电率；这两种作用均被抗氧化剂阻断，并被化学氧化剂模拟。高碳酸血症刺激了60个神经元中的32个（53%）。值得注意的是，这些CO2/H+-化学敏感神经元对HBO2优先敏感；90%对HBO2和/或化学氧化剂敏感的神经元也对CO2/H+化学敏感。相反，只有19%的hbo2不敏感神经元对CO2/H+化学敏感。我们得出结论，高氧降低了膜电导，并通过O-2自由基机制刺激了假定的中央CO2/H+-化学受体神经元的放电。这些发现也许可以解释为什么高氧刺激通气。
Hyperoxia, a model of oxidative stress, can disrupt brain stem function, presumably by an increase in O-2 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 O-2 free radical mechanism. These findings may explain why hyperoxia, paradoxically, stimulates ventilation.