Calbindin-D28k fails to protect hippocampal neurons against ischemia in spite of its cytoplasmic calcium buffering properties:: Evidence from calbindin-D28k knockout mice
Calbindin-D28k fails to protect hippocampal neurons against ischemia in spite of its cytoplasmic calcium buffering properties:: Evidence from calbindin-D28k knockout mice
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DOI：
10.1016/s0306-4522(97)00632-5
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发表时间：
1998-07-01
期刊：
影响因子：
3.3
通讯作者：
Mody, I
中科院分区：
文献类型：
--
作者：
Klapstein, GJ;Vietla, S;Mody, I
细胞质钙结合蛋白被认为可以保护神经元免受过量Ca2+升高引起的损伤。然而，从理论上讲，移动的细胞Ca2+缓冲液也可以通过促进Ca2+在细胞质中的快速分散来促进神经元损伤。与对照组形成鲜明对比的是，在缺乏钙结合蛋白- d -28k基因的小鼠中，海马CA1锥体神经元的突触反应在体外短暂缺氧葡萄糖剥夺后恢复得更快、更完全，并且在体内颈动脉闭塞12分钟后持续的细胞损伤更少。calbinding -d -28k缺陷小鼠的其他细胞和突触特性，如动作电位放电适应性的改变，以及受影响突触成对脉冲和频率增强的改变，与神经元内Ca2+缓冲的缺失是一致的。我们的研究结果为calbinding - d -28k的神经保护作用提供了直接的实验证据。(c) 1998 ibro。Elsevier Science Ltd.出版。
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-D-28k, 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 iii 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-D-28k-deficient mice were consistent with a missing intraneuronal Ca2+ buffer.Our findings provide direct experimental evidence against a neuroprotective role for calbindin-D-28k. (C) 1998 IBRO. Published by Elsevier Science Ltd.