Hayat Shaista, Wigley Caroline B, Robbins Jon
Neural Damage and Repair GroupCentre for Neuroscience Research, King's College London, Guys Campus, SE1 1UL, London, UK
Mol Cell Neurosci. 2003 Feb;22(2):259-70. doi: 10.1016/s1044-7431(03)00051-4.
Intracellular calcium handling by rat olfactory ensheathing cells (OECs) is implicated in their support for regrowth of adult CNS neurites in a coculture model of axonal regeneration. Pretreatment of OECs with BAPTA-AM to sequester glial intracellular calcium (Ca(2+)) reduces significantly the numbers of cocultured neurons regrowing neurites. The mean resting Ca(2+) of OECs cultured alone or with neurons was 300 nM in an external solution containing 2.5 mM calcium (Ca(2+)). In high K(+) or zero Ca(2+), resting Ca(2+) significantly decreased. Ca(2+) significantly increased when Ca(2+) was increased to 20 mM, lonomycin, thapsigargin, and thimerosal increased Ca(2+), and caffeine, ryanodine, and cyclopiazonic acid were without effect. Of the receptor agonists tested, none induced a change in Ca(2+). The calcium influx induced by high Ca(2+) was blocked by La(3+) and SKF96365, partially inhibited by Cd(2+), and insensitive to Ni(2+) and nifedipine. Pretreatment of OECs with La(3+) reduced neurite regrowth in cocultures in a concentration-dependent manner over the range that blocked the non-voltage-gated calcium flux through a putative TRP-like channel, which, we propose, is activated in OEC-mediated axonal regeneration.
在轴突再生的共培养模型中，大鼠嗅鞘细胞（OECs）的细胞内钙处理与它们对成年中枢神经系统（CNS）神经突再生的支持作用有关。用BAPTA-AM预处理OECs以螯合神经胶质细胞内钙（Ca(2+)），可显著减少共培养的再生神经突的神经元数量。在含有2.5 mM钙（Ca(2+)）的外部溶液中，单独培养或与神经元一起培养的OECs的平均静息Ca(2+)为300 nM。在高K(+)或零Ca(2+)条件下，静息Ca(2+)显著降低。当Ca(2+)增加到20 mM时，Ca(2+)显著增加，离子霉素、毒胡萝卜素和硫柳汞可增加Ca(2+)，而咖啡因、ryanodine和环匹阿尼酸则无作用。在所测试的受体激动剂中，没有一种能诱导Ca(2+)发生变化。高Ca(2+)诱导的钙内流被La(3+)和SKF96365阻断，被Cd(2+)部分抑制，对Ni(2+)和硝苯地平不敏感。用La(3+)预处理OECs会以浓度依赖的方式降低共培养中的神经突再生，其浓度范围可阻断通过假定的类TRP通道的非电压门控钙通量，我们认为该通道在OEC介导的轴突再生中被激活。
