A novel potassium channel in skeletal muscle mitochondria

A novel potassium channel in skeletal muscle mitochondria
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DOI:
10.1016/j.bbabio.2008.05.007
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发表时间:
2008-07-01
影响因子:
4.3
通讯作者:
Kunz, Wolfram S.
Kunz, Wolfram S.
中科院分区:
生物学2区
文献类型:
--
作者:
Skalska, Jolanta;Piwonska, Marta;Kunz, Wolfram S.

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在这项工作中,我们提供了骨骼肌线粒体中潜在存在钾通道的证据。在分离的脂肪骨骼肌线粒体中,钙离子能够使线粒体内膜去极化,并以严格的钾依赖方式刺激呼吸。大电导钙激活钾通道(BKCa通道)的拮抗剂200 nM轮藻毒素或50 nM朱砂毒素可完全消除钙离子对钾离子的这种特异性效应。此外,BKCa通道开放剂NS1619模拟了钙对呼吸和线粒体膜电位的钾专一性影响。根据这些功能数据,光镜和电子显微镜、平面脂双层重建和免疫学研究证实,BKCa通道优先位于大鼠骨骼肌纤维的线粒体膜内。我们认为,由于通道开放剂NS1619保护成肌细胞系C2C12免受氧化损伤,开放BKCa通道激活线粒体K+转运对心肌保护可能是重要的。(C)2008爱思唯尔B.V.保留所有权利。
In this work we provide evidence for the potential presence of a potassium channel in skeletal muscle mitochondria. In isolated Fat skeletal muscle mitochondria, Ca2+ was able to depolarize the mitochondrial inner membrane and stimulate respiration in a strictly potassium-dependent manner. These potassium specific effects of Ca2+ were completely abolished by 200 nM charybdotoxin or 50 nM iberiotoxin, which are well-known inhibitors of large conductance, calcium-activated potassium channels (BKCa channel). Furthermore, NS1619, a BKCa-channel opener, mimicked the potassium-specific effects of calcium on respiration and mitochondrial membrane potential. In agreement with these functional data, light and electron microscopy, planar lipid bilayer reconstruction and immunological studies identified the BKCa channel to be preferentially located in the inner mitochondrial membrane of rat skeletal muscle fibers. We propose that activation of mitochondrial K+ transport by opening of the BKCa channel may be important for myoprotection since the channel opener NS1619 protected the myoblast cell line C2C12 against oxidative injury. (c) 2008 Elsevier B.V. All rights reserved.