TASK channels contribute to neuroprotective action of inhalational anesthetics.
TASK channels contribute to neuroprotective action of inhalational anesthetics.
复制标题
TASK 通道有助于吸入麻醉剂的神经保护作用。
DOI：
10.1038/srep44203
复制
发表时间：
2017-03-09
影响因子：
4.6
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Yao C;Li Y;Shu S;Yao S;Lynch C;Bayliss DA;Chen X
吸入性麻醉剂后处理可以减轻缺血再灌注脑损伤，尽管这种作用的细胞机制尚未确定。目前的研究旨在测试ASK通道是否有助于其神经保护作用。使用全细胞记录来检查挥发性麻醉剂对皮层神经元中的ASK电流的影响，并验证来自ASK −/−小鼠的麻醉剂激活的ASK电流的损失。采用大鼠大脑中动脉阻塞（tMCAO）模型建立脑缺血再灌注损伤模型。定量RT-PCR分析显示，在TASK−/−小鼠的皮质和海马中，TASK mRNA减少了>90%。tMCAO攻击后，ASK −/−小鼠的梗死区域比C57 BL/6 J小鼠大得多。缺血性损伤后给予异氟烷或七氟烷可降低C57 BL/6 J小鼠的脑梗死百分比和神经功能缺损评分，这些作用在ASK −/−小鼠中降低。全细胞记录显示，在来自野生型小鼠的皮质锥体神经元中观察到的异氟烷激活的背景钾电流在ASK −/−小鼠中显著降低。我们的研究表明，任务通道可以限制缺血-再灌注损伤的皮质，和挥发性麻醉剂的后处理提供神经保护作用，部分依赖于激活皮层神经元的任务电流。
Postconditioning with inhalational anesthetics can reduce ischemia-reperfusion brain injury, although the cellular mechanisms for this effect have not been determined. The current study was designed to test if TASK channels contribute to their neuroprotective actions. Whole cell recordings were used to examine effects of volatile anesthetic on TASK currents in cortical neurons and to verify loss of anesthetic-activated TASK currents from TASK−/− mice. A transient middle cerebral artery occlusion (tMCAO) model was used to establish brain ischemia-reperfusion injury. Quantitative RT-PCR analysis revealed that TASK mRNA was reduced by >90% in cortex and hippocampus of TASK−/− mice. The TASK−/− mice showed a much larger region of infarction than C57BL/6 J mice after tMCAO challenge. Isoflurane or sevoflurane administered after the ischemic insult reduced brain infarct percentage and neurological deficit scores in C57BL/6 J mice, these effect were reduced in TASK−/− mice. Whole cell recordings revealed that the isoflurane-activated background potassium current observed in cortical pyramidal neurons from wild type mice was conspicuously reduced in TASK−/− mice. Our studies demonstrate that TASK channels can limit ischemia-reperfusion damage in the cortex, and postconditioning with volatile anesthetics provides neuroprotective actions that depend, in part, on activation of TASK currents in cortical neurons.