Klapstein G J, Vietla S, Lieberman D N, Gray P A, Airaksinen M S, Thoenen H, Meyer M, Mody I
Department of Neurology, UCLA School of Medicine RNRC 3-131, Los Angeles, CA 90095-1769, USA.
Neuroscience. 1998 Jul;85(2):361-73. doi: 10.1016/s0306-4522(97)00632-5.
Cytoplasmic calcium-binding proteins are thought to shield neurons against damage induced by excessive Ca2+ elevations. Yet, in theory, a mobile cellular Ca2+ buffer could just as well promote neuronal injury by facilitating the rapid dispersion of Ca2+ throughout the cytoplasm. In sharp contrast to controls, in mice lacking the gene for calbindin-D28k, synaptic responses of hippocampal CA1 pyramidal neurons which are normally extremely vulnerable to ischemia, recovered significantly faster and more completely after a transient oxygen-glucose deprivation in vitro, and sustained less cellular damage following a 12 min carotid artery occlusion in vivo. Other cellular and synaptic properties such as the altered adaptation of action potential firing, and altered paired-pulse and frequency potentiation at affected synapses in calbindin-D28k-deficient mice were consistent with a missing intraneuronal Ca2+ buffer. Our findings provide direct experimental evidence against a neuroprotective role for calbindin-D28k.
细胞质钙结合蛋白被认为可保护神经元免受过量钙离子升高所诱导的损伤。然而，从理论上讲，一种可移动的细胞内钙离子缓冲剂同样可能通过促进钙离子在整个细胞质中的快速扩散而加剧神经元损伤。与对照组形成鲜明对比的是，在缺乏钙结合蛋白-D28k基因的小鼠中，海马CA1锥体神经元的突触反应（这些神经元通常对缺血极其敏感）在体外短暂氧糖剥夺后恢复得明显更快、更完全，并且在体内12分钟颈动脉闭塞后细胞损伤持续时间更短。钙结合蛋白-D28k缺陷小鼠中其他细胞和突触特性，如动作电位发放适应性改变以及受影响突触处配对脉冲和频率增强改变，与细胞内缺失钙离子缓冲剂一致。我们的研究结果提供了直接的实验证据，反驳了钙结合蛋白-D28k具有神经保护作用的观点。
