Konrad T, Beier K, Kusterer K, Juchem R, Usadel K H, Angermüller S
Department of Internal Medicine I, University of Frankfurt/Main, Germany.
Histochem J. 1997 Apr;29(4):309-15. doi: 10.1023/a:1026426615130.
Calcium channel blockers protect cells against ischaemia-reperfusion injury. In the present study, the effect of verapamil on mitochondrial calcium content was investigated in situ in normoxic, hypoxic and reoxygenated rat liver. Subcellular distribution of exchangeable calcium ions, which form an electron-dense precipitate with antimonate, was demonstrated with the glutaraldehyde-osmium antimonate technique. Calcium precipitates were quantified morphometrically using automatic image analysis. In normoxic liver, the mitochondrial calcium content formed a gradient decreasing from the periportal to perivenous regions. The low mitochondrial calcium content in perivenous regions remained unaffected in all experimental conditions. In hypoxic and reoxygenated liver, the calcium content in mitochondria of the periportal areas was significantly reduced. Verapamil pretreatment levelled the calcium gradient in normoxic liver by reducing the periportal calcium content. Verapamil had no effect on the mitochondrial calcium content in hypoxic liver. In contrast, in verapamil-pretreated reoxygenated liver, the mitochondrial calcium content in periportal mitochondria increased significantly, thus restoring the zonal calcium gradient. In conclusion, these data suggest that modulations of mitochondrial calcium content in the periportal region of the liver lobule may play an important role in the protective effects of verapamil against ischaemia-reperfusion injury.
钙通道阻滞剂可保护细胞免受缺血再灌注损伤。在本研究中，在常氧、缺氧及复氧的大鼠肝脏中对维拉帕米对线粒体钙含量的影响进行了原位研究。采用戊二醛-锇锑酸盐技术显示了可交换钙离子的亚细胞分布，可交换钙离子与锑酸盐形成电子致密沉淀。使用自动图像分析对钙沉淀进行形态计量学定量。在常氧肝脏中，线粒体钙含量形成从门静脉周围到肝静脉周围区域递减的梯度。在所有实验条件下，肝静脉周围区域低的线粒体钙含量均未受影响。在缺氧和复氧的肝脏中，门静脉周围区域线粒体中的钙含量显著降低。维拉帕米预处理通过降低门静脉周围的钙含量使常氧肝脏中的钙梯度趋于平缓。维拉帕米对缺氧肝脏中的线粒体钙含量无影响。相反，在维拉帕米预处理的复氧肝脏中，门静脉周围线粒体中的线粒体钙含量显著增加，从而恢复了区域钙梯度。总之，这些数据表明肝小叶门静脉周围区域线粒体钙含量的调节可能在维拉帕米对缺血再灌注损伤的保护作用中发挥重要作用。
