Berg-Johnsen J, Grøndahl T O, Langmoen I A, Haugstad T S, Hegstad E
Institute for Surgical Research, National Hospital, Oslo, Norway.
Neurol Res. 1995 Jun;17(3):201-8. doi: 10.1080/01616412.1995.11740313.
Excessive release of glutamate is believed to play a major role in the susceptibility of neurons to ischaemia. Whether the glutamate release is the primary event or occurs in response to electrophysiologic alterations has not been clarified. In the present study, the amino acid release was therefore correlated to changes in electrophysiological parameters and energy status during conditions of low oxygen tension and varying glucose concentrations in rat hippocampal slices. Plain hypoxia failed to produce glutamate release. All neurons underwent, however, a slow depolarization causing most of the neurons to lose their membrane potential within 10 minutes. By restoring the membrane potential to resting level by current injection, the neurons could still be activated synaptically and respond to transmitter application. Following reoxygenation most of the cells regained their resting membrane potential, but showed reduced excitability. When the slices were exposed to hypoxia combined with glucose deprivation (simulated ischaemia), there was a pronounced increase in the glutamate release. This glutamate release was always preceded by a fast anoxic depolarization. Whereas hypoxia reduced the ATP content only to approximately 50%, ATP was depleted in slices exposed to simulated ischaemia. The results demonstrate that although the neurons lose their membrane potential completely during hypoxia, there is no glutamate release. A fast anoxic depolarization provoked by simulated ischaemia, however, is always followed by glutamate release, probably due to a more severe ATP depletion.
谷氨酸的过度释放被认为在神经元对缺血的易感性中起主要作用。谷氨酸释放是原发性事件还是对电生理改变的反应，目前尚未明确。因此，在本研究中，在大鼠海马切片低氧张力和不同葡萄糖浓度条件下，氨基酸释放与电生理参数和能量状态的变化相关。单纯缺氧未能导致谷氨酸释放。然而，所有神经元都经历了缓慢的去极化，导致大多数神经元在10分钟内失去膜电位。通过电流注入将膜电位恢复到静息水平后，神经元仍可被突触激活并对递质应用作出反应。复氧后，大多数细胞恢复了静息膜电位，但兴奋性降低。当切片暴露于缺氧并伴有葡萄糖剥夺（模拟缺血）时，谷氨酸释放明显增加。这种谷氨酸释放总是先出现快速的缺氧去极化。虽然缺氧仅使ATP含量降低至约50%，但在暴露于模拟缺血的切片中ATP被耗尽。结果表明，虽然神经元在缺氧期间完全失去膜电位，但没有谷氨酸释放。然而，模拟缺血引发的快速缺氧去极化总是伴随着谷氨酸释放，这可能是由于更严重的ATP耗竭所致。
