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Brain‐derived neurotrophic factor triggers a rapid glutamate release through increase of intracellular Ca 2+ and Na + in cultured cerebellar neurons
Author(s) -
Numakawa T.,
Matsumoto T.,
Adachi N.,
Yokomaku D.,
Kojima M.,
Takei N.,
Hatanaka H.
Publication year - 2001
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.1201
Subject(s) - glutamate receptor , brain derived neurotrophic factor , intracellular , neurotrophic factors , metabotropic glutamate receptor , nmda receptor , chemistry , biophysics , biology , endocrinology , microbiology and biotechnology , medicine , biochemistry , receptor
We reported previously that BDNF induced glutamate release was dependent on intracellular Ca 2+ but not extracellular Ca 2+ 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 Ca 2+ and Na + in cerebellar neurons, and investigated the possibility of reverse transport of glutamate mediated by BDNF. As reported, BDNF increased the intracellular Ca 2+ level. We found that the Ca 2+ increase induced by BDNF was completely blocked by xestospongin C, an IP 3 receptor antagonist, and U‐73122, a PLC‐γ inhibitor. Xestospongin C and U‐73122 also blocked the BDNF‐dependent glutamate release, suggesting that the BDNF‐induced transient increase of Ca 2+ through the activation of the PLC‐γ/ IP 3 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 Ca 2+ 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‐β‐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‐γ/IP 3 ‐mediated Ca 2+ signaling. J. Neurosci. Res. 66:96–108, 2001. © 2001 Wiley‐Liss, Inc.