Brain-derived neurotrophic factor triggers a rapid glutamate release through increase of intracellular Ca2+ and Na+ in cultured cerebellar neurons

被引:52
作者
Numakawa, T
Matsumoto, T
Adachi, N
Yokomaku, D
Kojima, M
Takei, N
Hatanaka, H
机构
[1] Osaka Univ, Inst Prot Res, Div Prot Biosynthesis, Suita, Osaka 5650871, Japan
[2] Niigata Univ, Brain Res Inst, Dept Mol Neurobiol, Niigata, Japan
关键词
glutamate release; glutamate transporter; calcium increase; sodium influx; phospholipase C-gamma;
D O I
10.1002/jnr.1201
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We reported previously that BDNF induced glutamate release was dependent on intracellular Ca2+ but not extracellular Ca2+ in cerebellar neurons (Numakawa et al., 1999). It was revealed that the release was through a non-exocytotic pathway (Takei et al., 1998; Numakawa et al., 1999). In the present study, we monitored the dynamics of intracellular Ca2+ and Na+ in cerebellar neurons, and investigated the possibility of reverse transport of glutamate mediated by BDNF. As reported, BDNF increased the intracellular Ca2+ level. We found that the Ca2+ increase induced by BDNF was completely blocked by xestospongin C, an IP3 receptor antagonist, and U-73122, a PLC-gamma inhibitor. Xestospongin C and U-73122 also blocked the BDNF-dependent glutamate release, suggesting that the BDNF-induced transient increase of Ca2+ through the activation of the PLC-gamma/ IP3 pathway was essential for the glutamate release. We found that BDNF induced a Na+ influx. This was blocked by treatment with TTX. U-73122 and xestospongin C blocked the BDNF-induced Na+ influx, suggesting that the Na+ influx required the BDNF-induced Ca2+ increase. Next, we examined the possibility that a co-transporter of Na+ and glutamate was involved in the BDNF-induced glutamate release. BDNF-induced glutamate release was blocked by L-trans-pyrollidine-2,4-dicalboxylic acid (t-PDC), a glutamate transporter inhibitor, whereas neither the 4-aminopyridine (4AP)- nor high potassium (HK+)induced release was blocked by t-PDC. In addition, DL-threo-beta -benzyloxyaspartate (DL-TBOA) also blocked the BDNF-mediated glutamate release, suggesting that reverse transport of glutamate may be involved. All the results therefore suggest that Na+-dependent reverse transport contributes to BDNF-mediated transmitter release through the PLC-gamma /IP3-mediated Ca2+ signaling. (C) 2001 Wiley-Liss, Inc.
引用
收藏
页码:96 / 108
页数:13
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