期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：10
页码：6157-6162
DOI：10.1073/pnas.1031598100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Recent evidence suggests that intracellular Zn2+ accumulation contributes to the neuronal injury that occurs in epilepsy or ischemia in certain brain regions, including hippocampus, amygdala, and cortex. Although most attention has been given to the vesicular Zn2+ that is released into the synaptic space and may gain entry to postsynaptic neurons, recent studies have highlighted pools of intracellular Zn2+ that are mobilized in response to stimulation. One such Zn2+ pool is likely bound to cytosolic proteins, like metallothioneins. Applying imaging techniques to cultured cortical neurons, this study provides novel evidence for the presence of a mitochondrial pool distinct from the cytosolic protein or ligand-bound pool. These pools can be pharmacologically mobilized largely independently of each other, with Zn2+ release from one resulting in apparent net Zn2+ transfer to the other. Further studies found evidence for complex and potent effects of Zn2+ on isolated brain mitochondria. Submicromolar levels, comparable to those that might occur on strong mobilization of intracellular compartments, induced membrane depolarization (loss of {Delta}{psi}m), increases in currents across the mitochondrial inner membrane as detected by direct patch clamp recording of mitoplasts, increased O2 consumption and decreased reactive oxygen species (ROS) generation, whereas higher levels decreased O2 consumption and increased ROS generation. Finally, strong mobilization of protein-bound Zn2+ appeared to induce partial loss of {Delta}{psi}m, suggesting that movement of Zn2+ between cytosolic and mitochondrial pools might be of functional significance in intact neurons.
