Distinct types of ionic modulation of GABA actions in pyramidal cells and interneurons during electrical induction of hippocampal seizure-like network activity
Distinct types of ionic modulation of GABA actions in pyramidal cells and interneurons during electrical induction of hippocampal seizure-like network activity
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DOI：
10.1111/j.1460-9568.2007.05543.x
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发表时间：
2007-05-01
影响因子：
3.4
通讯作者：
Takada, Masahiko
中科院分区：
文献类型：
--
作者：
Fujiwara-Tsukamoto, Yoko;Isomura, Yoshikazu;Takada, Masahiko
最近的研究表明，在正常的细胞外液中，电刺激引起癫痫样后放电活动，而这种活动总是在GABA依赖的慢去极化之前进行的。这些后放电反应在成熟的海马神经元中是同步的，并受到兴奋性GABA能输入的驱动。然而，锥体细胞和中间神经元中的GABA能信号从超极化到去极化(甚至是兴奋性的)的瞬时转换机制的差异尚不清楚。为了阐明这种诱发后放电的快速GABA转换的网络机制，我们在体外研究了大鼠海马CA1区锥体细胞和/或中间神经元中GABA能反应的时间变化。锥体细胞组的慢去极化程度和GABA转化率明显大于中间神经元组。除了GABAA受体的激活外，离子型谷氨酸受体对神经元的兴奋还能促进锥体细胞内GABA的转化，从而诱导后电荷的产生。慢去极化包括两个不同的阶段：早期阶段主要依赖于GABAA介导的突触后氯离子积聚，晚期阶段主要依赖于细胞外K+积聚，这两个阶段都被谷氨酸能神经元兴奋所增强。此外，胞外K+的积累增强了后放电的每个振荡反应，可能是通过K+偶联的Cl-转运体进一步积累Cl-而实现的。我们的发现表明，在GABA和谷氨酸依赖的慢去极化过程中，GABA逆转电位可能主要通过双相氯离子侵入锥体细胞而高于其峰阈值，从而导致癫痫样活动的启动。
It has recently been shown that electrical stimulation in normal extracellular fluid induces seizure-like afterdischarge activity that is always preceded by GABA-dependent slow depolarization. These afterdischarge responses are synchronous among mature hippocampal neurons and driven by excitatory GABAergic input. However, the differences in the mechanisms whereby the GABAergic signals in pyramidal cells and interneurons are transiently converted from hyperpolarizing to depolarizing (and even excitatory) have remained unclear. To clarify the network mechanisms underlying this rapid GABA conversion that induces afterdischarges, we examined the temporal changes in GABAergic responses in pyramidal cells and/or interneurons of the rat hippocampal CA1 area in vitro. The extents of slow depolarization and GABA conversion were much larger in the pyramidal cell group than in any group of interneurons. Besides GABAA receptor activation, neuronal excitation by ionotropic glutamate receptors enhanced GABA conversion in the pyramidal cells and consequent induction of afterclischarge. The slow depolarization was confirmed to consist of two distinct phases; an early phase that depended primarily on GABAA-mediated postsynaptic Cl- accumulation, and a late phase that depended on extracellular K+ accumulation, both of which were enhanced by glutamatergic neuron excitation. Moreover, extracellular K+ accumulation augmented each oscillatory response of the afterdischarge, probably by further Cl- accumulation through K+-coupled Cl- transporters. Our findings suggest that the GABA reversal potential may be elevated above their spike threshold predominantly in the pyramidal cells by biphasic Cl- intrusion during the slow depolarization in GABA- and glutamate-dependent fashion, leading to the initiation of seizure-like epileptiform activity.