Takeda Atsushi, Minami Akira, Sakurada Naomi, Nakajima Satoko, Oku Naoto
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
Neurochem Int. 2007 Jan;50(2):322-7. doi: 10.1016/j.neuint.2006.08.015. Epub 2006 Oct 25.
The response of hippocampal mossy fiber zinc to excessive glutamate release was examined to understand the role of the zinc in excessive excitation in the hippocampus. Extracellular zinc and glutamate concentrations during excessive stimulation with high K(+) were compared between the hippocampal CA3 and CA1 by the in vivo microdialysis. Zinc concentration in the CA3 was more increased than that in the CA1, while glutamate concentration in the CA3 was less increased than that in the CA1. It is likely that more increase in extracellular zinc is linked with less increase in extracellular glutamate in the CA3. To see zinc action in mossy fiber synapses during excessive excitation, furthermore, 1mM glutamate was regionally delivered to the stratum lucidum in the presence of zinc or CaEDTA, a membrane-impermeable zinc chelator, and intracellular calcium signal was measured in the CA3 pyramidal cell layer. The persistent increase in calcium signal during stimulation with glutamate was significantly attenuated in the presence of 100 microM zinc, while significantly enhanced in the presence of 1mM CaEDTA. These results suggest that zinc released from mossy fibers attenuates the increase in intracellular calcium signal in mossy fiber synapses and postsynaptic CA3 neurons after excessive inputs to dentate granular cells.
为了解锌在海马体过度兴奋中的作用，研究了海马体苔藓纤维锌对过量谷氨酸释放的反应。通过体内微透析比较了海马体CA3区和CA1区在高钾过度刺激期间的细胞外锌和谷氨酸浓度。CA3区的锌浓度比CA1区增加得更多，而CA3区的谷氨酸浓度比CA1区增加得更少。CA3区细胞外锌的更多增加可能与细胞外谷氨酸的较少增加有关。此外，为了观察过度兴奋期间苔藓纤维突触中的锌作用，在存在锌或CaEDTA（一种膜不可渗透的锌螯合剂）的情况下，将1mM谷氨酸局部递送至透明层，并在CA3锥体细胞层测量细胞内钙信号。在存在100μM锌的情况下，谷氨酸刺激期间钙信号的持续增加显著减弱，而在存在1mM CaEDTA的情况下显著增强。这些结果表明，在齿状颗粒细胞受到过量输入后，苔藓纤维释放的锌会减弱苔藓纤维突触和突触后CA3神经元中细胞内钙信号的增加。
