Tymianski M
Playfair Neuroscience Unit, University of Toronto, Ontario, Canada.
Adv Neurol. 1996;71:85-105.
Although the concept of Ca2+ ions as mediators of cytotoxicity has been accepted, there have been past difficulties in correlating intra-cellular Ca2+ levels and neurotoxicity. It is now apparent that neurons that succumb to Ca2+ loading sustain a failure of Ca2+ homeostatic mechanisms due to processes set into motion very early following the initial insult. Recent work suggests that there exists a linear correlation between total neuronal Ca2+ loading and neurodegeneration. However, the slope of this linear relationship may be modulated by numerous factors such as the transmembrane Ca2+ gradient, the route of Ca2+ influx, and the presence of various Ca2+ buffering and extrusion systems within the cell. In the future, processes responsible for neurodegeneration may be better understood through the study of the subcellular interplay between membrane receptors, second messenger systems, and Ca2+ buffering mechanisms. Refinements on past techniques will be necessary to place further quantitative boundaries on global and subcellular neurotoxic Ca2+ increases.
尽管钙离子作为细胞毒性介质的概念已被接受，但过去在将细胞内钙离子水平与神经毒性联系起来方面存在困难。现在很明显，因钙离子负荷而受损的神经元由于在初始损伤后很早就启动的过程，导致钙离子稳态机制失效。最近的研究表明，神经元总的钙离子负荷与神经退行性变之间存在线性关系。然而，这种线性关系的斜率可能会受到多种因素的调节，如跨膜钙离子梯度、钙离子内流途径以及细胞内各种钙离子缓冲和外排系统的存在。未来，通过研究膜受体、第二信使系统和钙离子缓冲机制之间的亚细胞相互作用，可能会更好地理解导致神经退行性变的过程。有必要改进过去的技术，以便对整体和亚细胞水平上神经毒性钙离子增加的情况进一步划定定量界限。
