Faghihi Mahdieh, Sukhodub Andriy, Jovanovic Sofija, Jovanovic Aleksandar
Maternal and Child Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK.
Int J Mol Med. 2008 Jan;21(1):69-73.
Although Mg2+ reduces infarct size in whole heart models of ischaemia/reperfusion, the cardioprotective effect of Mg2+ at the cellular level is still a controversial issue. Therefore, we tested whether Mg2+ protects cardiomyocytes against ischaemia. To accomplish this aim we used an experimental model of ischaemia that utilises single beating adult cardiomyocytes in which oxygen tension is tightly regulated without the use of oxygen scavengers or metabolic inhibitors. Taking all these into consideration, this model is probably closer to in vivo conditions than the majority of previously published cellular models of ischaemia. We found that the addition of extracellular Mg2+ (8 mM) increased the survival of cells exposed to ischaemia. As sarcolemma and mitochondria are end-effectors of cardioprotective signalling, we examined whether Mg2+ regulates sarcolemmal and mitochondrial events. Mg2+ (8 mM) did not affect the whole cell K+ current as revealed by patch clamp electrophysiology. Experiments with laser confocal microscopy and the mitochondrial membrane potential-sensitive dye, JC-1, showed that Mg2+ (8 mM) did not affect ischaemia-induced mitochondrial membrane depolarisation. However, a significantly lower JC-1 ratio was required to kill cells under control conditions than cells treated with Mg2+ (8 mM). Based on the obtained data, we conclude that Mg2+ protects single beating cardiomyocytes against ischaemia by increasing cellular resistance to the consequences of mitochondrial membrane depolarisation in the cytosol.
尽管镁离子（Mg2+）在心肌缺血/再灌注的全心脏模型中可减小梗死面积，但Mg2+在细胞水平的心脏保护作用仍是一个有争议的问题。因此，我们测试了Mg2+是否能保护心肌细胞免受缺血损伤。为实现这一目标，我们使用了一种缺血实验模型，该模型利用成年单搏动心肌细胞，在不使用氧清除剂或代谢抑制剂的情况下严格调节氧张力。综合考虑所有这些因素，该模型可能比大多数先前发表的细胞缺血模型更接近体内情况。我们发现，添加细胞外Mg2+（8 mM）可提高暴露于缺血环境下的细胞存活率。由于肌膜和线粒体是心脏保护信号的终效应器，我们研究了Mg2+是否调节肌膜和线粒体事件。膜片钳电生理学显示，Mg2+（8 mM）不影响全细胞钾电流。激光共聚焦显微镜和线粒体膜电位敏感染料JC-1的实验表明，Mg2+（8 mM）不影响缺血诱导的线粒体膜去极化。然而，在对照条件下杀死细胞所需的JC-1比率明显低于用Mg2+（8 mM）处理的细胞。基于获得的数据，我们得出结论，Mg2+通过增加细胞对细胞质中线粒体膜去极化后果的抵抗力，保护单搏动心肌细胞免受缺血损伤。
