Amaral Michelle D, Pozzo-Miller Lucas
Department of Neurobiology, Civitan International Research Center and McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
J Neurosci. 2007 May 9;27(19):5179-89. doi: 10.1523/JNEUROSCI.5499-06.2007.
Brain-derived neurotrophic factor (BDNF) exerts prominent effects on hippocampal neurons, but the mechanisms that initiate its actions are poorly understood. We report here that BDNF evokes a slowly developing and sustained nonselective cationic current (I(BDNF)) in CA1 pyramidal neurons. These responses require phospholipase C, IP3 receptors, Ca2+ stores, and Ca2+ influx, suggesting the involvement of transient receptor potential canonical subfamily (TRPC) channels. Indeed, I(BDNF) is absent after small interfering RNA-mediated TRPC3 knockdown. The sustained kinetics of I(BDNF) appears to depend on phosphatidylinositol 3-kinase-mediated TRPC3 membrane insertion, as shown by surface biotinylation assays. Slowly emerging membrane currents after theta burst stimulation are sensitive to the scavenger TrkB-IgG and TRPC inhibitors, suggesting I(BDNF) activation by evoked released of endogenous, native BDNF. Last, TRPC3 channels are necessary for BDNF to increase dendritic spine density. Thus, TRPC channels emerge as novel mediators of BDNF-mediated dendritic remodeling through the activation of a slowly developing and sustained membrane depolarization.
脑源性神经营养因子（BDNF）对海马神经元具有显著作用，但其启动作用的机制尚不清楚。我们在此报告，BDNF在CA1锥体神经元中引发一种缓慢发展且持续的非选择性阳离子电流（I(BDNF)）。这些反应需要磷脂酶C、IP3受体、Ca2+储存和Ca2+内流，提示瞬时受体电位香草酸亚家族（TRPC）通道参与其中。事实上，小干扰RNA介导的TRPC3基因敲低后I(BDNF)消失。如表面生物素化分析所示，I(BDNF)的持续动力学似乎依赖于磷脂酰肌醇3激酶介导的TRPC3膜插入。θ波爆发刺激后缓慢出现的膜电流对清除剂TrkB-IgG和TRPC抑制剂敏感，提示内源性天然BDNF的诱发释放激活了I(BDNF)。最后，TRPC3通道是BDNF增加树突棘密度所必需的。因此，TRPC通道通过激活缓慢发展且持续的膜去极化，成为BDNF介导的树突重塑的新型介质。
