Mitochondrial BKCa channel.

Mitochondrial BKCa channel.
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DOI:
10.3389/fphys.2015.00104
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发表时间:
2015
影响因子:
4
通讯作者:
Toro L
Toro L
中科院分区:
医学2区
文献类型:
--
作者:
Balderas E;Zhang J;Stefani E;Toro L

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自15年前在神经胶质瘤细胞系中发现线粒体BKCa通道(mitoBKCa)以来,已经在脑细胞和心肌细胞中进行了研究,所述脑细胞和心肌细胞具有一般生物物理特性,例如高K+电导(~300 pS)、电压依赖性和Ca 2+敏感性。在破译mitoBKCa分子组成方面的主要进展包括确定它是由Kcnma 1基因编码的,C末端剪接插入物赋予mitoBKCa靶向心脏线粒体的能力,以及其与β亚基潜在共组装的证据。众所周知,β1亚基直接与细胞色素c氧化酶相互作用,并且mitoBKCa可以通过呼吸链的底物进行调节。mitoBKCa通道在保护心脏免受缺血方面具有核心作用,其中通道的药理学活化影响活性氧物质和线粒体Ca 2+的产生,可能通过阻碍线粒体过渡孔的不受控制的打开来防止细胞死亡。支持这一观点,用伊比利亚毒素抑制mitoBKCa,增强细胞色素c从神经胶质瘤线粒体的释放。许多诱人的问题仍然悬而未决。其中一些是:mitoBKCa是如何与呼吸链结合的?mitoBKCa是否在线粒体生理学中发挥非传导作用?哪些是mitoBKCa的功能伙伴?mitoBKCa在其他细胞类型中的作用是什么?这些问题的答案是必不可少的,以确定线粒体生物学和疾病的mitoBKCa通道的影响。
Since its discovery in a glioma cell line 15 years ago, mitochondrial BKCa channel (mitoBKCa) has been studied in brain cells and cardiomyocytes sharing general biophysical properties such as high K+ conductance (~300 pS), voltage-dependency and Ca2+-sensitivity. Main advances in deciphering the molecular composition of mitoBKCa have included establishing that it is encoded by the Kcnma1 gene, that a C-terminal splice insert confers mitoBKCa ability to be targeted to cardiac mitochondria, and evidence for its potential coassembly with β subunits. Notoriously, β1 subunit directly interacts with cytochrome c oxidase and mitoBKCa can be modulated by substrates of the respiratory chain. mitoBKCa channel has a central role in protecting the heart from ischemia, where pharmacological activation of the channel impacts the generation of reactive oxygen species and mitochondrial Ca2+ preventing cell death likely by impeding uncontrolled opening of the mitochondrial transition pore. Supporting this view, inhibition of mitoBKCa with Iberiotoxin, enhances cytochrome c release from glioma mitochondria. Many tantalizing questions remain open. Some of them are: how is mitoBKCa coupled to the respiratory chain? Does mitoBKCa play non-conduction roles in mitochondria physiology? Which are the functional partners of mitoBKCa? What are the roles of mitoBKCa in other cell types? Answers to these questions are essential to define the impact of mitoBKCa channel in mitochondria biology and disease.
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