Activation of DOR attenuates anoxic K+ derangement via inhibition of Na+ entry in mouse cortex
Activation of DOR attenuates anoxic K+ derangement via inhibition of Na+ entry in mouse cortex
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DOI：
10.1093/cercor/bhm247
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发表时间：
2008-09-01
期刊：
影响因子：
3.7
通讯作者：
Xia, Ying
中科院分区：
文献类型：
--
作者：
Chao, Dongman;Bazzy-Asaad, Alia;Xia, Ying
我们最近发现，在小鼠大脑皮层，阿片受体(DOR)的激活可以减轻缺氧或缺糖引起的K+稳态的破坏。这一新的观察结果表明，DOR可能通过调节K+稳态来保护神经元免受缺氧/缺血损伤，因为K+稳态的破坏在缺氧/缺血应激下的神经元损伤中起着关键作用。本研究旨在探讨DOR神经保护作用的离子机制。由于缺氧导致Na+内流，从而刺激K+外漏，我们研究了DOR是否通过靶向Na+基K+外漏来保护皮层免受缺氧性K+紊乱的影响。在小鼠皮层脑片上使用V敏感微电极，我们发现：1)降低Na+浓度并用不透性的N-甲基-D-葡萄糖胺替代可引起浓度依赖性的缺氧性K+紊乱的减弱；2)用通透性Li+替代降低Na+浓度有增强缺氧性K+紊乱的趋势；3)低Na+灌流对缺氧性K+反应的保护作用在很大程度上被低Na+灌流所消除，无论被取代的阳离子是什么。我们认为，外源性Na+浓度对缺氧性K+的紊乱有很大影响，DOR的激活可能会减弱由Na+激活机制引起的缺氧性K+紊乱。
We have recently found that in the mouse cortex, activation of delta-opioid receptor (DOR) attenuates the disruption of K+ homeostasis induced by hypoxia or oxygen-glucose deprivation. This novel observation suggests that DOR may protect neurons from hypoxic/ischemic insults via the regulation of K+ homeostasis because the disruption of K+ homeostasis plays a critical role in neuronal injury under hypoxic/ischemic stress. The present study was performed to explore the ionic mechanism underlying the DOR-induced neuroprotection. Because anoxia causes Na+ influx and thus stimulates K+ leakage, we investigated whether DOR protects the cortex from anoxic K+ derangement by targeting the Na+-based K+ leakage. By using V-sensitive microelectrodes in mouse cortical slices, we showed that 1) lowering Na+ concentration and substituting with impermeable N-methyl-D-glucamine caused a concentration-dependent attenuation of anoxic K+ derangement; 2) lowering Na+ concentration by substituting with permeable Li+ tended to potentiate the anoxic K+ derangement; and 3) the DOR-induced protection against the anoxic K+ responses was largely abolished by low-Na+ perfusion irrespective of the substituted cation. We conclude that external Na+ concentration greatly influences anoxic K+ derangement and that DOR activation likely attenuates anoxic K+ derangement induced by the Na+-activated mechanisms in the cortex.