Glutamate-induced intracellular calcium changes and neurotoxicity in cortical neuronsin vitro: Effect of chemical ischemia

Glutamate-induced intracellular calcium changes and neurotoxicity in cortical neuronsin vitro: Effect of chemical ischemia
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谷氨酸诱导的细胞内钙变化和体外皮质神经元的神经毒性:化学缺血的影响

DOI:
10.1016/0306-4522(94)90468-5
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发表时间:
1994
期刊:
影响因子:
3.3
通讯作者:
I.J Reynolds
I.J Reynolds
中科院分区:
医学3区
文献类型:
--
作者:
S. Rajdev;I.J Reynolds

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为了研究钙在缺血期间神经元死亡中的作用,我们检查了在正常和缺血条件下暴露于谷氨酸(3 μM + 1 μM 甘氨酸)、NMDA(30 μM + 1 μM 甘氨酸)、红藻氨酸(100 μM)或高 K+(50 mM)5 分钟的单个大鼠前脑神经元的细胞内 Ca2+([Ca2+]i) 变化特征。测量的[Ca2+]i变化参数包括峰值[Ca2+]i水平、平台[Ca2+]i水平、[Ca2+]响应曲线下面积以及[Ca2+]i恢复到峰值响应的10%所需的时间。在正常条件下,所有研究的激动剂都产生相似的[Ca2+i变化。应用无葡萄糖缓冲液中的 5 mM KCN 模拟化学缺血,对 [Ca2+]i 的基础水平没有影响,但显着增强和延长所有激动剂产生的 [Ca2+]i 变化。然而,在毒性研究中,化学缺血仅显着增强谷氨酸和N-甲基-d-天冬氨酸的毒性。在相关研究中,所有死亡的神经元在丧失活力之前都表现出不可逆的继发[Ca2+iload]。这些研究表明,虽然Ca2+进入可能在神经元死亡中发挥关键作用,但初始[Ca2+]i变化的幅度并不能预测皮质神经元中激动剂的毒性。
To study the role of calcium in neuronal death during ischemia, we examined the characteristics of intracellular Ca2+([Ca2+]i) changes in single rat forebrain neurons exposed for 5 min to glutamate (3 μM + 1 μM glycine), NMDA (30 μM + 1 μM glycine), kainate (100 μM) or high K+(50 mM), under both normal and ischemie conditions. The parameters of [Ca2+]ichange measured included peak [Ca2+]ilevel, plateau [Ca2+]ilevel, area under the [Ca2+]iresponse curve and time taken by [Ca2+]ito recover to 10% of the peak response. Under normal conditions, all the agonists studied produced similar [Ca2+ichanges. Chemical ischemia simulated by application of 5 mM KCN in glucose-free buffer had no effect on the basal level of [Ca2+]i, but significantly enhanced and prolonged the [Ca2+ichanges produced by all the agonists. However, in toxicity studies, chemical ischemia significantly potentiated the toxicity of only glutamate andN-methyl-d-aspartate. In correlation studies, all the neurons which died displayed an irreversible secondary [Ca2+iload prior to loss of viability.These studies suggest that while Ca2+entry may play a critical role in neuronal death, the magnitude of initial [Ca2+]ichange does not predict the toxicity of an agonist in cortical neurons.
DOI: --
发表时间: 1986
影响因子: --
作者:
J. Olney;Collins Rc;Sloviter Rs
通讯作者: J. Olney;Collins Rc;Sloviter Rs
DOI: 10.1126/science.2543080
发表时间: 1989-06-09
期刊: SCIENCE
影响因子: 56.9
作者:
JONES, OT;KUNZE, DL;ANGELIDES, KJ
通讯作者: ANGELIDES, KJ
DOI: 10.1126/science.2157282
发表时间: 1990-03-23
期刊: SCIENCE
影响因子: 56.9
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通讯作者: CHOI, DW
DOI: --
发表时间: 1989-08
期刊: The Journal of pharmacology and experimental therapeutics
影响因子: --
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Dean M. Hartley;D. Choi
通讯作者: Dean M. Hartley;D. Choi