Neurotrophin-evoked depolarization requires the sodium channel NaV1.9
Neurotrophin-evoked depolarization requires the sodium channel NaV1.9
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DOI：
10.1038/nature01085
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发表时间：
2002-10-17
期刊：
影响因子：
64.8
通讯作者：
Konnerth, A
中科院分区：
文献类型：
--
作者：
Blum, R;Kafitz, KW;Konnerth, A
脑源性神经营养因子（BDNF）和其他神经营养因子对正常的脑功能至关重要。中枢神经系统中的许多类型的神经元被BDNF或神经营养因子-4/5兴奋，这一作用最近被认为与突触可塑性有关。神经营养因子的这种递质样作用的机制尚不清楚。在这里，通过筛选候选基因的反义信使RNA表达的方法，并通过共表达受体酪氨酸激酶TrkB和各种钠通道，我们证明，河豚毒素不敏感的钠通道Na（V）1.9神经营养素诱发的兴奋的基础。这些结果建立了神经营养素诱发的去极化的分子基础，并揭示了配体介导的钠通道激活的机制。
Brain-derived neurotrophic factor (BDNF) and other neurotrophins are essential for normal brain function. Many types of neurons in the central nervous system are excited by BDNF or neurotrophin-4/5, an action that has recently been implicated in synaptic plasticity. The mechanisms involved in this transmitter-like action of neurotrophins remains unclear. Here, by screening candidate genes with an antisense messenger RNA expression approach and by co-expressing the receptor tyrosine kinase TrkB and various sodium channels, we demonstrate that the tetrodotoxin-insensitive sodium channel Na(V)1.9 underlies the neurotrophin-evoked excitation. These results establish the molecular basis of neurotrophin-evoked depolarization and reveal a mechanism of ligand-mediated sodium channel activation.