Mitani A, Namba S, Ikemune K, Yanase H, Arai T, Kataoka K
Department of Physiology, School of Medicine, Ehime University, Japan.
J Cereb Blood Flow Metab. 1998 Oct;18(10):1088-98. doi: 10.1097/00004647-199810000-00005.
Glutamate receptor-mediated responses were investigated by using a whole-cell recording and an intracellular calcium ion ([Ca2+]i) imaging in gerbil postischemic hippocampal slices prepared at 1, 3, 6, 9, 12, and 24 hours after 5-minute ischemia. Bath application of N-methyl-D-aspartic acid (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and kainate showed that NMDA-, AMPA- and kainate-induced currents were enhanced in postischemic CA1 pyramidal neurons at 1 to 12 hours after 5-minute ischemia. NMDA and non-NMDA receptor-mediated excitatory postsynaptic currents (EPSC) were examined in postischemic CA1 pyramidal neurons at 3 hours after 5-minute ischemia to confirm whether synaptic responses are enhanced in the postischemic CA1 pyramidal neurons. The amplitudes of NMDA- and non-NMDA-receptor-mediated EPSC were enhanced in the postischemic CA1 pyramidal neurons. NMDA-, AMPA-, and kainate-induced [Ca2+]i elevations were also examined to determine whether the enhancement of currents is accompanied by the enhancement of [Ca2+]i elevation. The enhancements of NMDA-, AMPA-, and kainate-induced [Ca2+]i elevations were shown in the postischemic CA1. These results indicate that NMDA and non-NMDA receptor-mediated responses are persistently enhanced in the CA1 pyramidal neurons 1 to 12 hours after transient ischemia, and suggest that the enhancement of glutamate receptor-mediated responses may act as one of crucial factors in the pathologic mechanism responsible for leading postischemic CA1 pyramidal neurons to irreversible neuronal injury.
在沙土鼠缺血5分钟后1、3、6、9、12和24小时制备的缺血后海马切片中，采用全细胞膜片钳记录和细胞内钙离子（[Ca2+]i）成像技术研究了谷氨酸受体介导的反应。通过灌流应用N-甲基-D-天冬氨酸（NMDA）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和海人藻酸发现，在缺血5分钟后1至12小时，缺血后CA1锥体神经元中NMDA、AMPA和海人藻酸诱导的电流增强。在缺血5分钟后3小时，对缺血后CA1锥体神经元中的NMDA和非NMDA受体介导的兴奋性突触后电流（EPSC）进行检测，以确认缺血后CA1锥体神经元的突触反应是否增强。缺血后CA1锥体神经元中NMDA和非NMDA受体介导的EPSC幅度增强。还检测了NMDA、AMPA和海人藻酸诱导的[Ca2+]i升高，以确定电流增强是否伴随着[Ca2+]i升高的增强。在缺血后CA1中显示出NMDA、AMPA和海人藻酸诱导的[Ca2+]i升高增强。这些结果表明，在短暂缺血后1至12小时，CA1锥体神经元中NMDA和非NMDA受体介导的反应持续增强，提示谷氨酸受体介导反应的增强可能是导致缺血后CA1锥体神经元发生不可逆神经元损伤的病理机制中的关键因素之一。
