文献阅读报告TRPCchannels.ppt

Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor NATURE | VOL 434 | 14 APRIL 2005 文献阅读报告 中国学者的又一丰硕成果 阐明发育过程中神经纤维生长方向是如何被“引导”和“调控”的，是当前神经生物学关注的前沿问题之一。 生长中的神经纤维的最前段，有一个形如倒锥体被称为“生长锥”的结构，它具有像变形虫一样的高度动态，时刻像一个准备出击的“战士”，活跃地探索细胞外的环境，感受外界导向因子，引导神经纤维朝特定的方向生长，逐步形成神经网络。 一、前 言 如果把神经纤维的生长比喻成一辆前进的汽车，那么，其前端结构“生长锥”如同一个“导航仪”——它活跃地探索细胞外环境，捕捉各种导向信号，然后引导“汽车”正确生长前进，逐步形成大脑神经网络。 但是，在这一过程中导向因子如何“引导”神经生长方向的分子机理此前尚未完全揭示。 此次袁小兵和王以政研究员及其学生李艳、贾怡昌等应用生长锥转向分析方法，首次观察到神经细胞外的导向因子---一种称为BDNF的蛋白质，在把信号传递到细胞膜内过程中，能打开TRPC（transient receptor potential channel,瞬时受体电位通道），促使神经纤维最前段生长锥内的钙离子浓度增加，从而能引导神经纤维朝BDNF浓度高的一侧方向生长。 该研究揭示了引导神经信号需要激发钙通透的离子通道---TRPC这类阳离子通道新的功能，这将对研究神经损伤再生机制提供新的启发，国外同行审稿人认为，“这是一项做得很好也很重要的研究”。 二、结果赏析 BDNF gradient caused marked growth-cone turning towards the pipette within 30 min. 1. The guidance of nerve growth cone by BDNF BDNF 2. The chem-attractive effect of BDNF required TrkB and Ca2+ The chemo-attractive effect of BDNF abolished by K252a , an inhibitor of TrkB . abolished in a Ca2+-free medium, blocked by BAPTA-AM, a membrane permeable Ca2+ buffer, blocked by TG, which depletes intracellular Ca2+ stores. 1). The chemo-attractive effect of BDNF required activation of the high-affinity BDNF receptor TrkB; 2). Ca2+ influx through plasma membrane Ca2+ channels and Ca2+ release from internal stores are both required for growth-cone turning induced by BDNF. BDNF-induced growth-cone attraction unaffected by nifedipine (specific blocker of L--type VDCCs conotoxin MVIIC (specific blocker of P/Q-type VDCCs) Ryanodine at a high concentration (blocks ryanodine-sensitive channels ) Saxitoxin (blocker of Na+-channel) 3). Ca2+ influx through VDCCs and internal Ca2+ release through ryanodine channels are unlikely to contribute to BDNF-induced growth-cone turning. 4). Na+-channel-dependent depolarization is not involved in BDNF-induced growth-cone turning. 3.The involvement of Ca2+-permeant TRPC channel