LOW EXTRACELLULAR MAGNESIUM INDUCES EPILEPTIFORM ACTIVITY AND SPREADING DEPRESSION IN RAT HIPPOCAMPAL SLICES
LOW EXTRACELLULAR MAGNESIUM INDUCES EPILEPTIFORM ACTIVITY AND SPREADING DEPRESSION IN RAT HIPPOCAMPAL SLICES
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DOI：
10.1152/jn.1987.57.3.869
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发表时间：
1987-03-01
影响因子：
2.5
通讯作者：
HEINEMANN, U
中科院分区：
文献类型：
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作者：
MODY, I;LAMBERT, JDC;HEINEMANN, U
在大鼠海马切片中研究了低细胞外 Mg2+ 浓度 ([Mg2+]o) 对神经元活动的影响。用不含 Mg2+ 的培养基灌注 20-40 分钟后，当 [Mg2+]o 下降至约 0.1-0.4 mM 时，CA1 和 CA3 区域会产生自发场电位，但齿状回不会产生自发场电位。在 CA3 锥体细胞层中，这些电位由重复的 (0.3–0.5 Hz)、40 到 120 毫秒长的正偏转 (2–5 mV) 和叠加的群体尖峰组成。在 CA1 区域的金字塔层（str.）中，观察到持续 30-80 ms 的正负偏转（小于 3 mV），其发生频率为 0.3-0.5 Hz。在某些情况下，还观察到持续时间较长且快速重复的事件。在 CA3 锥体细胞中，场电位瞬变的细胞内相关性是 20 至 30 mV 阵发性去极化位移 (PDS)，并叠加动作电位突发，随后是大的（大于 10 mV）、500 至 1,200 ms 长的后超极化 (AHP)。相比之下，CA1区的锥体神经元没有表现出PDS；相反，兴奋性突触后电位（EPSP）/抑制性突触后电位（IPSP）序列伴随着瞬时场电位变化。有时，在没有任何场电位瞬变的情况下，也可以在 CA1 中观察到以高频率发生的自发 EPSP/IPSP。在两个海马区域，尽管动作电位阈值降低了 2 至 5 mV，但癫痫样活动的发展并未使神经元的静息膜电位 (RMP) 和输入电阻 (RN) 发生显着改变。通过将细胞外 Ca2+ 浓度 ([Ca2+]o) 从 1.6 mM 提高到 3.6 mM，可以轻松抑制无 Mg2+ 培养基中的自发活动。 10-30微米的DL-2-氨基-5-磷酸戊酸（2-APV）（N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体拮抗剂）的灌注也减弱或可逆地阻断自发活动。通过手术将 CA1 区与 CA3 区隔离，可以阻止 CA1 区瞬变的发生，但不能阻止 CA3 区瞬变的发生。在没有[Mg2+]o的情况下，突触输入/输出曲线向左移动。引发群体峰值的阈值强度是正常培养基中阈值强度的 50-75%。成对脉冲促进仍然存在于阈值附近，但在较高刺激强度下减弱。通过重复刺激 Schaffer 侧支/连合通路（20 Hz/5-10 秒）产生的 [Ca2+]o 减少，并通过 CA1 区域的离子选择性微电极进行监测，在无 Mg2+ 培养基中得到增强。（摘要截断为 400 字）
The effect of low extracellular Mg2+ concentration ([Mg2+]o) on neuronal activity was studied in rat hippocampal slices. After 20–40 min of perfusion with Mg2+-free medium, when [Mg2+]o declined to approximately 0.1–0.4 mM, spontaneous field potentials developed in the CA1 and CA3 regions, but not in the dentate gyrus. In the CA3 pyramidal cell layer, these potentials consisted of repetitive (0.3–0.5 Hz), 40- to 120-ms-long positive deflections (2–5 mV) with superimposed population spikes. In the stratum (str.) pyramidale of the CA1 region, positive-negative deflections (less than 3 mV) lasting for 30–80 ms were observed, which occurred with a frequency of 0.3-0.5 Hz. In some cases, longer lasting and rapidly recurring events were also observed. In CA3 pyramidal cells, the intracellular correlates of the field potential transients were 20- to 30-mV paroxysmal depolarization shifts (PDS) with superimposed bursts of action potentials, followed by large (greater than 10 mV), 500- to 1,200-ms-long afterhyperpolarizations (AHP). In contrast, pyramidal neurons of the CA1 area did not show PDSs; instead, sequences of excitatory postsynaptic potentials (EPSPs)/inhibitory postsynaptic potentials (IPSPs) accompanied the transient field potential changes. Occasionally, spontaneous EPSPs/IPSPs, occurring with high frequencies, could also be observed in CA1 without any field potential transients. In both hippocampal regions, the epileptiform activity evolved without significant alterations in the resting membrane potential (RMP) and input resistance (RN) of the neurons, although a 2- to 5-mV reduction in action potential threshold was noted. The spontaneous activity in Mg2+-free medium was readily suppressed by raising the extracellular Ca2+ concentration ([Ca2+]o) from 1.6 to 3.6 mM. The perfusion of 10-30 microns DL-2-amino-5-phosphonovaleric acid (2-APV), an antagonist for the glutamate receptors of the N-methyl-D-aspartate (NMDA) type, also attenuated or reversibly blocked the spontaneous activity. Surgical isolation of area CA1 from CA3 ceased the occurrence of the transients in CA1 but not in CA3. The synaptic input/output curves were shifted to the left in the absence of [Mg2+]o. Threshold intensity for eliciting population spikes was 50-75% of that in normal medium. Paired-pulse facilitation was still present near threshold, but was reduced at higher stimulus intensities. Decreases in [Ca2+]o, produced by repetitive stimulation (20-Hz/5-10 s) of the Schaffer collateral/commissural pathway and monitored with ion-selective microelectrodes in the CA1 region, were enhanced in Mg2+-free medium.(ABSTRACT TRUNCATED AT 400 WORDS)