| 11599006 |
Numakawa T, Matsumoto T, Adachi N, Yokomaku D, Kojima M, Takei N, Hatanaka H: Brain-derived neurotrophic factor triggers a rapid glutamate release through increase of intracellular Ca (2+) and Na (+) in cultured cerebellar neurons. J Neurosci Res. 2001 Oct 1;66(1):96-108.
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-gamma 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-gamma/ 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-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/IP (3)-mediated Ca (2+) signaling. |
10(0,0,0,10) |