Brain-derived neurotrophic factor induces long-lasting Ca2+-activated K+ currents in rat visual cortex neurons
Brain-derived neurotrophic factor induces long-lasting Ca2+-activated K+ currents in rat visual cortex neurons
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DOI：
10.1046/j.1460-9568.2002.02198.x
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发表时间：
2002-10-01
影响因子：
3.4
通讯作者：
Nabekura, J
中科院分区：
文献类型：
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作者：
Mizoguchi, Y;Monji, A;Nabekura, J
脑源性神经营养因子 (BDNF) 增加突触后细胞内 Ca2+ 并调节各种类型神经元的突触传递。 Ca2+ 激活的 K+ 电流主要由细胞内 Ca2+ 升高打开，有助于动作电位后的超极化并调节突触传递。我们询问 BDNF 是否通过大鼠急性分离的视觉皮层神经元中细胞内 Ca2+ 的突触后升高来诱导 Ca2+ 激活的 K+ 电流。使用制霉菌素穿孔膜片钳技术和使用 fura-2 进行细胞内 Ca2+ 动员成像来分析电流。在 -50 mV 的保持电位下，应用 BDNF (20 ng/mL) 1-2 分钟会诱导外向电流 (IBDNF-OUT；80.0 +/- 29.0 pA)，持续超过 90 分钟，每个测试的神经元均无衰减。 K252a (200 nM)（一种 Trk 受体酪氨酸激酶抑制剂）和 U73122 (3 muM)（一种特异性磷脂酶 C (PLC)-gamma 抑制剂）完全抑制 IBDNF-OUT。 IBDNF-OUT\对charybdotoxin-(600nM)和apamin-(300nM)敏感，表明该电流由Ca2+激活的K+通道携带。 BAPTA-AM (150 muM) 逐渐抑制 IBDNF-OUT。 Fura-2 成像显示，短暂应用 BDNF 会引起细胞内 Ca2+ 的持久升高。这些结果表明，BDNF 通过大鼠视觉皮层神经元细胞内 Ca2+ 的持续升高来诱导持久的 Ca2+ 激活的 K+ 电流。虽然 BDNF 可能通过 Trk B 受体发挥作用，对于通过细胞内 Ca2+ 升高诱导持久的 Ca2+ 激活 K+ 电流是必需的，但 BDNF 对于维持该电流不是必需的。
Brain-derived neurotrophic factor (BDNF) increases postsynaptic intracellular Ca2+ and modulates synaptic transmission in various types of neurons. Ca2+-activated K+ currents, opened mainly by intracellular Ca2+ elevation, contribute to hyperpolarization following action potentials and modulate synaptic transmission. We asked whether BDNF induces Ca2+ activated K+ currents by postsynaptic elevation of intracellular Ca2+ in acutely dissociated visual cortex neurons of rats. Currents were analysed using the nystatin-perforated patch clamp technique and imaging of intracellular Ca2+ mobilization with fura-2. At a holding potential of -50 mV, BDNF application (20 ng/mL) for 1-2 min induced an outward current (IBDNF-OUT; 80.0 +/- 29.0 pA) lasting for more than 90 min without attenuation in every neuron tested. K252a (200 nM), an inhibitor of Trk receptor tyrosine kinase, and U73122 (3 muM), a specific phospholipase C (PLC)-gamma inhibitor, suppressed IBDNF-OUT completely. IBDNF-OUT\ was both charybdotoxin- (600 nM) and apamin- (300 nM) sensitive, suggesting that this current was carried by Ca2+-activated K+ channels. BAPTA-AM (150 muM) gradually suppressed IBDNF-OUT. Fura-2 imaging revealed that a brief application of BDNF elicited a long-lasting elevation of intracellular Ca2+. These results show that BDNF induces long-lasting Ca2+-activated K+ currents by sustained intracellular Ca2+ elevation in rat visual cortex neurons. While BDNF, likely acting through the Trk B receptor, was necessary for the induction of long-lasting Ca2+-activated K+ currents via intracellular Ca2+ elevation, BDNF was not necessary for the maintenance of this current.