THE CALCIUM-CHANNEL BLOCKER NIFEDIPINE ATTENUATES SLOW EXCITATORY AMINO-ACID NEUROTOXICITY
THE CALCIUM-CHANNEL BLOCKER NIFEDIPINE ATTENUATES SLOW EXCITATORY AMINO-ACID NEUROTOXICITY
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DOI：
10.1126/science.2157282
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发表时间：
1990-03-23
期刊：
影响因子：
56.9
通讯作者：
CHOI, DW
中科院分区：
文献类型：
--
作者：
WEISS, JH;HARTLEY, DM;CHOI, DW
高浓度的N-甲基-D-天冬氨酸(NMDA)激动剂在暴露几分钟后就会引发培养的小鼠皮质神经元退化；相比之下，选择性的非NMDA激动剂或低水平的NMDA激动剂需要暴露几个小时才能引起类似的损伤。二氢吡啶钙通道拮抗剂硝苯地平被用来测试这种缓慢的神经毒性是否由电压门控通道的钙内流介导。硝苯地平对短暂暴露于高浓度NMDA引起的广泛神经元变性几乎没有影响，但显著减轻了24小时暴露于次最大浓度的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸盐、海人藻酸盐或喹啉酸盐所产生的神经毒性。钙离子通过二氢吡啶敏感的电压依赖性钙通道内流可能是NMDA或非NMDA谷氨酸受体长时间激活所致神经元损伤的重要环节。
High concentrations of potent N-methyl-D-aspartate (NMDA) agonists can trigger degeneration of cultured mouse cortical neurons after an exposure of only a few minutes; in contrast, selective non-NMDA agonists or low levels of NMDA agonists require exposures of several hours to induce comparable damage. The dihydropyridine calcium channel antagonist nifedipine was used to test whether this slow neurotoxicity is mediated by a calcium influx through voltage-gated channels. Nifedipine had little effect on the widespread neuronal degeneration induced by brief exposure to high concentrations of NMDA but substantially attenuated the neurotoxicity produced by 24-hour exposure to submaximal concentrations of .alpha.-amino-3-hydroxy-5-methyl-4-isoxazole propionate, kainate, or quinolinate. Calcium ion influx through dihydropyridine-sensitive, voltage-dependent calcium channels may be an important step in the neuronal injury induced by the prolonged activation of NMDA or non-NMDA glutamate receptors.