Differential effects of zinc on glutamatergic and GABAergic neurotransmitter systems in the hippocampus
Differential effects of zinc on glutamatergic and GABAergic neurotransmitter systems in the hippocampus
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DOI：
10.1002/jnr.10846
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发表时间：
2004-01
影响因子：
4.2
通讯作者：
A. Takeda;A. Minami;Yumiko Seki;N. Oku
中科院分区：
文献类型：
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作者：
A. Takeda;A. Minami;Yumiko Seki;N. Oku
大脑中约10%的锌存在于谷氨酸能神经元的突触囊泡中；然而，对囊泡锌的功能了解甚少。采用体内微透析法研究了锌对大鼠海马兴奋性和抑制性神经传递的突触前作用。10-300 μM ZnCl2灌注海马CA3区后，灌注液中谷氨酸水平降低，γ -氨基丁酸（GABA）水平升高。内源性锌与CaEDTA螯合后，灌注液中谷氨酸水平升高，而GABA水平降低，提示释放到突触间隙的锌对CA3区谷氨酸能神经元和GABA能神经元的作用不同。锌对GABA水平的升高可被2,3‐二氧‐6‐硝基‐1,2.3‐4‐四氢苯并(f)喹啉‐7‐磺胺（NBQX）拮抗，NBQX是α‐氨基‐3‐羟基‐5‐甲基‐4‐异恶唑丙酸盐(AMPA)/kainate受体的拮抗剂，但不受MK801的影响，MK801是N‐甲基‐D‐天冬氨酸（NMDA）受体的拮抗剂，维拉帕米是电压依赖性钙通道的阻滞剂。目前的研究表明，锌通过增强CA3区域的AMPA/kainate受体来增强GABA的释放，随后减少同一区域的突触前谷氨酸释放。锌似乎是谷氨酸释放的抑制性神经调节剂。©2003 Wiley‐Liss, Inc。
Approximately 10% of total zinc in the brain exists in synaptic vesicles of glutamatergic neurons; however, the function of vesicular zinc is poorly understood. The presynaptic action of zinc against excitatory and inhibitory neurotransmission was studied in rat hippocampus using in vivo microdialysis. When the hippocampal CA3 region was perfused with 10–300 μM ZnCl2, the level of glutamate in the perfusate was decreased, whereas the level of γ‐aminobutyric acid (GABA) was increased. Chelation of endogenous zinc with CaEDTA increased the glutamate level in the perfusate but decreased the GABA level, suggesting that zinc released into the synaptic cleft acts differentially on glutamatergic and GABAergic neurons in the CA3 region. The increase of GABA level by zinc was antagonized by 2,3‐dioxo‐6‐nitro‐1,2.3,4‐tetrahydrobenzo(f)quinoxaline‐7‐sulphonamide (NBQX), an antagonist of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)/kainate receptors, but not affected by MK801, an antagonist of N‐methyl‐D‐aspartate (NMDA) receptors, and verapamil, a blocker of voltage‐dependent calcium channels. The present study suggests that zinc enhances GABA release via potentiation of AMPA/kainate receptors in the CA3 region, followed by a decrease in presynaptic glutamate release in the same region. Zinc seems to be an inhibitory neuromodulator of glutamate release. © 2003 Wiley‐Liss, Inc.