Modulation of K2P3.1 (TASK-1), K2P9.1 (TASK-3), and TASK-1/3 heteromer by reactive oxygen species.
Modulation of K2P3.1 (TASK-1), K2P9.1 (TASK-3), and TASK-1/3 heteromer by reactive oxygen species.
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DOI：
10.1007/s00424-012-1159-y
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发表时间：
2012-11
影响因子：
4.5
通讯作者：
Kim, Donghee
中科院分区：
文献类型：
--
作者：
Papreck, Justin R.;Martin, Elizabeth A.;Lazzarini, Ping;Kang, Dawon;Kim, Donghee
由线粒体或NADPH氧化酶产生的活性氧（ROS）参与了化学感受器细胞缺氧对K+电流的抑制。由于TASK是这些细胞中高度活跃的背景K+通道，我们研究了ROS在缺氧诱导的TASK抑制中的作用。在HeLa细胞中表达TASKs，H2 O2应用于由内而外的补丁激活的ASK-1，ASK-3和ASK-1/3异源聚体开始在~16 mM。当应用于细胞附着或由外而外的补丁，326 mM H2 O2不影响ASK活性。其他K2 P通道（TREK-1、TREK-2、ASK-2、TALK-1、TRESK）不受H2 O2影响（检测浓度高达326 mM）。还原剂（二硫苏糖醇）和半胱氨酸修饰剂（MTSEA）对基本的ASK活性没有影响，也没有阻止过氧化氢诱导的通道活性增加。一个ASK突变体，其中的C-末端的ASK-3被替换为TREK-2的表现出正常的敏感性H2 O2。用于产生超氧自由基的黄嘌呤/黄嘌呤氧化酶混合物对来自膜两侧的ASK-1、ASK-3和ASK-1/3异聚体没有显示出影响，但强烈地激活来自细胞外侧的ASK-2。急性H2 O2（32-326 mM）暴露不影响HeLa细胞中hSlo 1/b1（BK）的表达和颈动脉体球细胞中BK。在颈动脉体球细胞、肾上腺皮质细胞和小脑颗粒神经元中，显示出丰富的缺氧敏感性ASK活性，H2 O2（>16 mM）仅在细胞内应用时激活通道，与克隆的ASK观察到的结果相似。这些发现表明，ROS不支持或抑制ASK和BK活性，因此不太可能是通过抑制这些K+通道引起细胞兴奋的缺氧信号。
Reactive oxygen species (ROS) generated by mitochondria or NADPH oxidase have been implicated in the inhibition of K+ current by hypoxia in chemoreceptor cells. As TASKs are highly active background K+ channels in these cells, we studied the role of ROS in hypoxia-induced inhibition of TASKs. In HeLa cells expressing TASKs, H2O2 applied to inside-out patches activated TASK-1, TASK-3 and TASK-1/3 heteromer starting at ~16 mM. When applied to cell-attached or outside-out patches, 326 mM H2O2 did not affect TASK activity. Other K2P channels (TREK-1, TREK-2, TASK-2, TALK-1, TRESK) were not affected by H2O2 (tested up to 326 mM). A reducing agent (dithiothreitol) and a cysteine-modifying agent (MTSEA) had no effect on basal TASK activity and did not block the H2O2-induced increase in channel activity. A TASK mutant in which the C-terminus of TASK-3 was replaced with that of TREK-2 showed a normal sensitivity to H2O2. Xanthine/xanthine oxidase mixture used to generate superoxide radical showed no effect on TASK-1, TASK-3 and TASK-1/3 heteromer from either side of the membrane, but strongly activated TASK-2 from the extracellular side. Acute H2O2 (32–326 mM) exposure did not affect hSlo1/b1(BK) expressed in HeLa cells and BK in carotid body glomus cells. In carotid body glomus cells, adrenal cortical cells and cerebellar granule neurons that show abundant hypoxia-sensitive TASK activity, H2O2 (>16 mM) activated the channels only when applied intracellularly, similar to that observed with cloned TASKs. These findings show that ROS do not support or inhibit TASK and BK activity, and therefore are unlikely to be the hypoxic signal that causes cell excitation via inhibition of these K+ channels.
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DOI：
10.1152/nips.01388.2002
发表时间：
2002-08-01
期刊：
NEWS IN PHYSIOLOGICAL SCIENCES
影响因子：
--
作者：
Archer, S;Michelakis, E
通讯作者：
Michelakis, E
DOI：
10.1152/ajpcell.2002.282.1.c27
发表时间：
2002-01-01
影响因子：
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作者：
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影响因子：
5.5
作者：
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影响因子：
2.3
作者：
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DOI：
10.1073/pnas.0507710103
发表时间：
2006-02-28
影响因子：
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作者：
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