Zinc inhibition of group I mGluR-mediated calcium homeostasis in auditory neurons

被引:34
作者
Zirpel, L [1 ]
Parks, TN [1 ]
机构
[1] Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA
来源
JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY | 2001年 / 2卷 / 02期
关键词
chick nucleus magnocellularis; metabotropic glutamate receptor;
D O I
10.1007/s101620010082
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Zinc is widely distributed in the central nervous system (CNS), it functions normally as a synaptic modulator, and it contributes to neuronal death under pathologic conditions. Zinc colocalizes with glutamate in excitatory synapses, and the presence of zinc is well characterized in the synapses of the auditory system. Since chick cochlear nucleus neurons depend upon synaptic activation of metabotropic glutamate receptors (mGluRs) for maintenance and survival, the goal of this study was to determine (1) if zinc is released from the eighth nerve calyces onto nucleus magnocellularis (NM) neurons in the chick cochlear nucleus, and, if so, (2) what effect it has on group I mGluR-mediated calcium homeostasis of these neurons. Using in vitro slices and a fluorescent dye relatively specific to vesicularized zinc, we show that zinc is indeed localized to the presynaptic calyces and is released upon nerve stimulation or KCI depolarization. Experiments employing fura-2 calcium imaging show that zinc inhibits group I mGluR release of calcium from internal stores of NM neurons and disrupts activity-dependent calcium homeostasis in a manner identical to the mGluR5-specific antagonist 2-methyl-6-(phenylethynyl) pyridine. The mGluR1-specific antagonist 7-hydroxyiminocyclopropan- [b]chromen-1a-carboxylic acid ethyl ester did not affect release of calcium from stores by the nonspecific mGluR agonist aminocyclopentane dicarboxylic acid, nor did it affect activity-dependent calcium homeostasis. We conclude that zinc is present in and released from the glutamatergic eighth nerve calyces. The presence of zinc inhibits mGluR5, a major component of calcium homeostasis of NM neurons, and plays a modulatory role in the activity-dependent, mGluR-mediated calcium homeostasis of auditory neurons.
引用
收藏
页码:180 / 187
页数:8
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