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[线粒体膜去极化后钙离子从线粒体的释放]

[Relese of Ca2+ from mitochondria after mitochondrial membrane depolarisation].

作者信息

Akopova O V, Sagach V F

出版信息

Ukr Biokhim Zh (1999). 2005 Sep-Oct;77(5):62-9.

Abstract

With the aid of specific inhibitors of Ca(2+)-uniporter (ruthenium red) and mitochondrial permeability transition pore, PTP (cyclosporine A) it is shown that PTP opening takes place after loading the rat liver mitochondria with calcium and depolarisation of mitochondrial membrane with protonophore (carbonyl cyanide m-chlorophenyl hydrazone, CCCP), and the pore opening accounts for accelerated efflux of calcium from mitochondrial matrix as well as availability of "rapid" component of two-exponential kinetic curve of Ca(2+)-efflux. An analysis of kinetic data of Ca2+ transport after membrane depolarisation also confirms our earlier observations that time frame of the pore open state is restricted, and membrane integrity is restored before all the calcium load is delivered into incubation medium. The absence of additivity between the shares of Ca(2+)-uniporter and PTP in Ca(2+)-transport is observed, and conclusion is made that partial share of PTP in calcium transport is not a constant, but a variable constituent which is diminished to zero as soon as the Ca(2+)-uniporter activity reaches its maximum after the abolition of membrane potential with CCCP. Based on some observations, it is supposed also that PTP inactivation takes place during calcium translocation across the mitochondrial membrane, which could account for limited release of Ca2+ from mitochondrial matrix through the pore itself as well as relatively narrow limits of the pore open state in comparison with time scale of complete cation release from depolarised mitochondria.

摘要

借助钙离子单向转运体的特异性抑制剂(钌红)和线粒体通透性转换孔(PTP)的抑制剂(环孢素A),研究表明,在大鼠肝线粒体加载钙以及用质子载体(羰基氰化物间氯苯腙,CCCP)使线粒体膜去极化后,PTP开放发生,且孔开放导致钙离子从线粒体基质加速外流,以及钙离子外流双指数动力学曲线中“快速”成分的出现。对膜去极化后钙离子转运动力学数据的分析也证实了我们之前的观察结果,即孔开放状态的时间框架是有限的,并且在所有钙负荷释放到孵育培养基之前,膜完整性就已恢复。观察到钙离子单向转运体和PTP在钙转运中的作用不存在加和性,并且得出结论,PTP在钙转运中的部分作用不是恒定的,而是一个可变的成分,一旦用CCCP消除膜电位后钙离子单向转运体活性达到最大值,该成分就会降至零。基于一些观察结果,还推测PTP失活发生在钙离子跨线粒体膜转运过程中,这可以解释线粒体基质中钙离子通过孔本身的有限释放,以及与去极化线粒体完全阳离子释放的时间尺度相比,孔开放状态的相对狭窄范围。

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