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首页> 外文期刊>American Journal of Physiology >The direct physiological effects of mitoK(ATP) opening on heart mitochondria.
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The direct physiological effects of mitoK(ATP) opening on heart mitochondria.

机译：mitoK（ATP）开放对心脏线粒体的直接生理作用。

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The mitochondrial ATP-sensitive K+ channel (mitoK(ATP)) has been assigned multiple roles in cell physiology and in cardioprotection. Each of these roles must arise from basic consequences of mitoK(ATP) opening that should be observable at the level of the mitochondrion. MitoK(ATP) opening has been proposed to have three direct effects on mitochondrial physiology: an increase in steady-state matrix volume, respiratory stimulation (uncoupling), and matrix alkalinization. Here, we examine the evidence for these hypotheses through experiments on isolated rat heart mitochondria. Using perturbation techniques, we show that matrix volume is the consequence of a steady-state balance between K+ influx, caused either by mitoK(ATP) opening or valinomycin, and K+ efflux caused by the mitochondrial K+/H+ antiporter. We show that increasing K+ influx with valinomycin uncouples respiration like a classical uncoupler with the important difference that uncoupling via K+ cycling soon causes rupture of the outer mitochondrial membrane and release of cytochrome c. By loading the potassium binding fluorescent indicator into the matrix, we show directly that K+ influx is increased by diazoxide and inhibited by ATP and 5-HD. By loading the fluorescent probe BCECF into the matrix, we show directly that increasing K+ influx with either valinomycin or diazoxide causes matrix alkalinization. Finally, by comparing the effects of mitoK(ATP) openers and blockers with those of valinomycin, we show that four independent assays of mitoK(ATP) activity yield quantitatively identical results for mitoK(ATP)-mediated K+ transport. These results provide decisive support for the hypothesis that mitochondria contain an ATP-sensitive K+ channel and establish the physiological consequences of mitoK(ATP) opening for mitochondria.
机译：线粒体ATP敏感的K +通道（mitoK（ATP））在细胞生理学和心脏保护中被赋予了多种作用。这些作用中的每一个都必须来自线粒体水平上应观察到的mitoK（ATP）开放的基本结果。有人提出MitoK（ATP）开放对线粒体生理有三个直接影响：稳态基质体积增加，呼吸刺激（解偶联）和基质碱化。在这里，我们通过对离体大鼠心脏线粒体进行实验来检验这些假设的证据。使用摄动技术，我们表明基质体积是由mitoK（ATP）开放或缬氨霉素引起的K +流入与线粒体K + / H +反向转运蛋白引起的K +外流之间稳态平衡的结果。我们显示，随着缬氨霉素增加的K +内流像经典的解偶联剂一样使呼吸解耦，但重要的区别在于通过K +循环解偶联很快会导致线粒体外膜破裂并释放细胞色素c。通过将钾结合荧光指示剂加载到基质中，我们直接显示出K +流入量被二氮嗪增加，并被ATP和5-HD抑制。通过将荧光探针BCECF加载到基质中，我们直接显示出与缬氨霉素或二氮嗪增加的K +流入量会引起基质碱化。最后，通过比较mitoK（ATP）开启剂和阻断剂与缬氨霉素的作用，我们显示mitoK（ATP）活性的四个独立测定产生的定量结果与mitoK（ATP）介导的K +转运相同。这些结果为线粒体包含一个ATP敏感的K +通道并确定线粒体的mitoK（ATP）开放的生理后果提供了决定性支持。

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