BK channel openers inhibit ROS production of isolated rat brain mitochondria
BK channel openers inhibit ROS production of isolated rat brain mitochondria
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DOI：
10.1016/j.expneurol.2008.05.004
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发表时间：
2008-08-01
影响因子：
5.3
通讯作者：
Kunz, Wolfram S.
中科院分区：
文献类型：
--
作者：
Kulawiak, Bogusz;Kudin, Alexei P.;Kunz, Wolfram S.
为了描述钾通道开放剂神经保护作用的潜在机制，我们研究了 Ca2+ 激活的大电导钾通道 (BKCa 通道) 开放剂如何影响大鼠脑线粒体活性氧 (ROS) 的产生，因为已知线粒体产生 ROS 对神经元存活具有至关重要的影响。我们研究了 BKCa 通道开放剂 CGS 7184 和 NS 1619 对离体大鼠脑线粒体过氧化氢产生率的影响。在含 K+ 的培养基中，3 μM 的两种通道开放剂可将过氧化氢生成率降低约 20%。在含 Na+ 的介质中未观察到这种效应。这种钾依赖性的过氧化氢产生部分抑制被发现对纳摩尔浓度的 BKCa 通道伊贝里奥毒素和卡里布毒素的选择性阻断剂敏感。综上所述，我们的数据与以下观点相一致：位于脑线粒体内膜的 Ca2+ 激活的大电导钾通道的开放会抑制呼吸链复合物 I 产生 ROS。这一发现可以解释 BK 钾通道开放剂对神经元存活的有益作用。 (C) 2008 Elsevier Inc. 保留所有权利。
To delineate the potential mechanism of neuroprotective effects of potassium channel openers we have investigated, how Ca2+-activated large conductance potassium channel (BKCa channel) openers influence the production of reactive oxygen species (ROS) by rat brain mitochondria, since mitochondrial generation of ROS is known to have a crucial influence on neuronal survival. We studied the effects of BKCa channel openers CGS 7184 and NS 1619 on hydrogen peroxide production rate of isolated rat brain mitochondria. In K+-containing media 3 mu M of both channel openers reduced the hydrogen peroxide production rates by approximately 20%. This effect was not observed in Na+-containing media. This potassium-dependent partial inhibition of hydrogen peroxide production was found to be sensitive to the selective blockers of BKCa channel iberiotoxin and charybdotoxin applied in nanomolar concentrations. Taken together, our data are compatible with the viewpoint that the opening of a Ca2+-activated large conductance potassium channel being localised in the inner membrane of brain mitochondria inhibits ROS production by respiratory chain complex I. This finding is suggested to explain the beneficial effects of BK potassium channel openers on neuronal survival. (C) 2008 Elsevier Inc. All rights reserved.