EPILEPTIFORM BURST ACTIVITY INDUCED BY POTASSIUM IN THE HIPPOCAMPUS AND ITS REGULATION BY GABA-MEDIATED INHIBITION
EPILEPTIFORM BURST ACTIVITY INDUCED BY POTASSIUM IN THE HIPPOCAMPUS AND ITS REGULATION BY GABA-MEDIATED INHIBITION
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DOI：
10.1152/jn.1987.57.1.325
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发表时间：
1987-01-01
影响因子：
2.5
通讯作者：
DINGLEDINE, R
中科院分区：
文献类型：
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作者：
KORN, SJ;GIACCHINO, JL;DINGLEDINE, R
从海马切片中的锥体神经元进行细胞内和细胞外记录，以研究通过将细胞外钾浓度从 3.5 mM 提高到 8.5 mM 诱导的自发阵发性爆发。所有海马亚区的细胞外记录表明，根据爆发起始判断，自发爆发似乎起源于 CA3c 或 CA3b 区域。爆发强度在 CA3b 和 CA3c 区域中也最大，并且向 CA2 区域逐渐减弱。细胞内记录表明，在 8.5 mM 钾浓度下，CA3c 神经元中总是存在大量的自发兴奋性突触后电位 (EPSP)、超极化后的大量爆发和膜电位的节律性超极化-去极化波。高钾 (8.5 mM) 诱导 CA3c 神经元中 GABA 能抑制性突触后电位 (IPSP) 的反转电位发生正向变化 (+9 mV)，而不会改变输入电阻或静息电位。这导致 IPSP 幅度急剧减小。 IPSP 振幅的降低发生在自发爆发之前，并且在恢复正常钾后可逆。描述了一种量化类似发作间期爆发放电相对强度的新技术。戊巴比妥、地西泮和 GABA 摄取抑制剂可增强 GABA 介导的突触抑制，降低钾诱导的爆发强度，而 GABA 拮抗剂荷包牡丹碱则增加爆发强度。二苯乙内酰脲和苯巴比妥这两种抗惊厥药对 GABA 能抑制作用不大，但对自发爆发没有作用。荷包牡丹碱和 4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇可降低爆发频率，但不受其他药物的影响。将切片温度从 35 摄氏度降低到 19 摄氏度会显着降低突发强度，但不会显着影响突发频率。我们假设高钾可能通过激活内向 KCl 泵或被动唐南效应诱导细胞内氯离子浓度升高，从而导致 IPSP 振幅降低。当抑制受到抑制时，高钾状态下出现的大量自发 EPSP 会导致单个 CA3c 神经元放电。 CA3c 细胞之间的突触和电相互作用的结合将放电同步为发作间期的尖峰爆发。
Intracellular and extracellular recordings were made from pyramidal neurons in hippocampal slices in order to study spontaneous paroxysmal bursting induced by raising the extracellular potassium concentration from 3.5 to 8.5 mM. Extracellular recordings from all hippocampal subfields indicated that spontaneous bursts appeared to originate in region CA3c or CA3b as judged by burst onset. Burst intensity was also greatest in regions CA3b and CA3c and became progressively less toward region CA2. Intracellular recordings indicated that in 8.5 mM potassium, large spontaneous excitatory postsynaptic potentials (EPSPs), large burst afterhyperpolarizations, and rhythmic hyperpolarizing-depolarizing waves of membrane potential were invariably present in CA3c neurons. High potassium (8.5 mM) induced a positive shift (+9 mV) in the reversal potential of GABAergic inhibitory postsynaptic potentials (IPSPs) in CA3c neurons without changing input resistance or resting potential. This resulted in a drastic reduction in amplitude of the IPSP. Reduction of IPSP amplitude occurred before the onset of spontaneous bursting and was reversible upon return to normal potassium. A new technique to quantify the relative intensity of interictal-like burst discharges is described. Pentobarbital, diazepam, and GABA uptake inhibitors, which enhance GABA-mediated synaptic inhibition, reduced the intensity of potassium-induced bursts, whereas the GABA antagonist bicuculline increased burst intensity. Diphenylhydantoin and phenobarbital, anticonvulsants that have little effect on GABAergic inhibition, were without effect on spontaneous bursts. Burst frequency was reduced by bicuculline and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol but was unaffected by other drugs. Reduction of slice temperature from 35 to 19 degrees C dramatically reduced burst intensity but did not markedly affect burst frequency. We hypothesize that high potassium induces a rise in intracellular chloride concentration, possibly by activating an inward KCl pump or by a passive Donnan effect, which results in a decreased IPSP amplitude. With inhibition suppressed, the large spontaneous EPSPs that appear in high potassium cause individual CA3c neurons to fire. A combination of synaptic and electrical interactions among CA3c cells then synchronizes discharges into interictal spike bursts.