Site of synaptic depression during hypoxia: a patch-clamp analysis.
Site of synaptic depression during hypoxia: a patch-clamp analysis.
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缺氧期间突触抑制的部位：膜片钳分析。
DOI：
10.1152/jn.1993.69.2.432
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发表时间：
1993
影响因子：
2.5
通讯作者：
Veregge,S
中科院分区：
文献类型：
--
作者：
Hershkowitz,N;Katchman,AN;Veregge,S
1. 用 16 至 23 日龄大鼠的海马切片研究缺氧对突触生理学的影响。通过全细胞膜片钳记录检查CA1锥体细胞，并通过将切片的灌注从含氧人工脑脊液(ACSF)切换到用95%N2-5%CO2饱和的ACSF来诱导缺氧。通过每 20 秒用辐射层中的电极刺激 Schaffer 侧副连合投射来评估突触反应。 2.缺氧发生后100-200秒内，CA1细胞顺向引发的突触反应很大程度上受到抑制。此外，在缺氧开始后观察到缓慢的内向电流。在所检查的 17 个细胞中，仅 2 个细胞观察到先于内向电流的瞬态外向电流。缺氧后约 140 秒，缓慢的内向电流在不可逆的快速内向电流中达到顶峰。这种快速的内向电流与通过场电位测量的扩散抑郁同时发生。河豚毒素（TTX）对该电流的发生没有影响，而犬尿酸则显着延迟其发生。 3.缺氧发生前，自发性瞬时内向电流明显。缺氧后这些事件的发生频率增加了三到四倍。瞬时内向电流在 TTX 中孵育的切片中持续存在，但在与混合 N-甲基-D-天冬氨酸 (NMDA)/非 NMDA 拮抗剂犬尿酸孵育的切片中几乎完全受到抑制。这将缺氧导致频率增加的自发事件确定为谷氨酸微型兴奋性突触后电流（mEPSC）。 4.当顺向引发的突触反应几乎完全被缺氧抑制时，mEPSC的平均振幅不受缺氧影响。此外，在几乎完全阻断突触反应的条件下，突触后细胞对谷氨酸压力喷射的反应并未受到抑制。因此，通过两项测量，突触后反应不受缺氧影响，表明缺氧引起的突触衰竭的部位位于突触前末端。 5.顺向引发的突触反应由 EPSC 和紧随其后的抑制性突触后电流 (IPSC) 组成。引起的突触后反应的 IPSC 部分比 EPSC 对缺氧的抑制更敏感。在一些细胞中，EPSC 在缺氧期间表现出单相振幅下降。然而，在大多数细胞中，EPSC 幅度最初下降，随后短暂增加并随后下降。（摘要截断为 400 字）
1. The effect of hypoxia on synaptic physiology was investigated in hippocampal slices from 16- to 23-day-old rats. CA1 pyramidal cells were examined by whole cell patch-clamp recording, and hypoxia was induced by switching perfusion of the slice from oxygenated artificial cerebrospinal fluid (ACSF) to ACSF saturated with 95% N2-5%CO2. Synaptic responses were assessed by stimulating the Schaffer collateral-commissural projection with an electrode in the stratum radiatum every 20 s. 2. Within 100-200 s of the onset of hypoxia, the orthrodromically elicited synaptic response of the CA1 cells was largely inhibited. In addition, a slow inward current was observed after the onset of hypoxia. A transient outward current, preceding the inward current, was observed in only 2 of 17 cells examined. The slow inward current culminated in an irreversible rapid inward current at approximately 140 s after hypoxia. This rapid inward current occurred simultaneously with spreading depression as measured by field potentials. Tetrodotoxin (TTX) had no effect on the onset of this current, whereas kynurenic acid significantly delayed its occurrence. 3. Before the onset of hypoxia, spontaneous transient inward currents were apparent. The frequency of these events increased by three- to fourfold after hypoxia. The transient inward currents persisted in slices incubated in TTX, but were almost completely inhibited in slices incubated with the mixed N-methyl-D-aspartate (NMDA)/non-NMDA antagonist kynurenic acid. This identified the spontaneous events that were increased in frequency by hypoxia as glutamatergic miniature excitatory postsynaptic currents (mEPSCs). 4. The mean amplitude of the mEPSCs was not affected by hypoxia at a time at which the orthodromically elicited synaptic response was almost completely inhibited by hypoxia. In addition, the response of the postsynaptic cell to pressure ejection of glutamate was not inhibited under conditions of nearly complete blocked the synaptic response. Thus, by two measures, the postsynaptic response was not affected by hypoxia, indicating that the site of hypoxia-induced synaptic failure was at the presynaptic terminal. 5. The orthodromically elicited synaptic response consisted of an EPSC followed closely by an inhibitory postsynaptic current (IPSC). The IPSC portion of the elicited postsynaptic response was more sensitive to inhibition by hypoxia than was the EPSC. In some cells the EPSC exhibited a monophasic decline in amplitude during hypoxia. However, in a majority of cells, an initial decline in the amplitude of the EPSC was followed by a transient increase and subsequent depression.(ABSTRACT TRUNCATED AT 400 WORDS)