TRPC3 channels are necessary for brain-derived neurotrophic factor to activate a nonselective cationic current and to induce dendritic spine formation
TRPC3 channels are necessary for brain-derived neurotrophic factor to activate a nonselective cationic current and to induce dendritic spine formation
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DOI：
10.1523/jneurosci.5499-06.2007
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发表时间：
2007-05-09
影响因子：
5.3
通讯作者：
Pozzo-Miller, Lucas
中科院分区：
文献类型：
--
作者：
Amaral, Michelle D.;Pozzo-Miller, Lucas
脑源性神经营养因子(BDNF)对海马神经元有显著的作用，但其作用机制尚不清楚。我们在这里报道了BDNF在CA1锥体神经元中引起缓慢发展和持续的非选择性阳离子电流(IBDNF)。这些反应需要磷脂酶C、IP3受体、钙储存和钙内流，提示瞬时受体潜在规范亚家族(TRPC)通道参与其中。事实上，在小干扰RNA介导的TRPC3被敲除后，IBDNF缺失。表面生物素化实验表明，IBDNF的持续动力学依赖于磷脂酰肌醇3-激酶介导的TRPC3膜插入。Theta Burst刺激后缓慢出现的膜电流对清除剂TrkB-Ig G和TRPC抑制剂敏感，提示IBDNF是通过诱导内源性天然BDNF的释放而激活的。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和持续的膜去极化，成为BDNF介导的树突状细胞重塑的新媒介。
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 (IBDNF) 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, IBDNF is absent after small interfering RNA-mediated TRPC3 knockdown. The sustained kinetics of IBDNF 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 IBDNF 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.