Participation of GABAA-mediated inhibition in ictallike discharges in the rat entorhinal cortex
Participation of GABAA-mediated inhibition in ictallike discharges in the rat entorhinal cortex
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DOI：
10.1152/jn.1998.79.1.352
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发表时间：
1998-01-01
影响因子：
2.5
通讯作者：
Avoli, M
中科院分区：
文献类型：
--
作者：
Lopantsev, V;Avoli, M
GABA介导的大鼠内嗅皮层癫痫样放电抑制的参与。神经生理学杂志。79：352-360，1998.自发的，同步活动诱导的4-氨基吡啶（4AP，50 μ M）在成年大鼠内嗅皮层进行了分析，同时举行的电位和细胞内记录在体外切片制备。四AP诱导孤立的负向场电位（发生间隔= 27.6 +/- 9.9）（SD）s;（a = 27个切片），对应于细胞内持久去极化（LLD）和由负场电位引发的癫痫样放电（发生间隔= 10.4 +/- 5.7 min; n = 27个切片）。用醋酸钾填充的微电极记录的LLD触发了几个可变幅度的动作电位，持续时间为1.7 +/- 0.8 s（n = 26个神经元），峰值幅度为11.8 +/- 5.0 mV（a = 26个神经元），逆转电位为-66.2 +/- 3.9 mV（n = 17个神经元）。用醋酸钾微电极研究的发作放电包括在强直和阵挛相期间具有动作电位放电的延长的去极化（持续时间= 72.9 +/- 44.3 s;峰值振幅= 29.2 +/- 11.4 mV; n = 25个神经元）。这些去极化具有-45.3 +/- 3.8 mV的逆转电位（n = 4个神经元）。KCl微电极的细胞内Cl-扩散使LLD和发作期去极化的幅度增加（分别为30.5 +/- 8.2 mV，n = 8和41.8 +/- 9.8 mV，n = 6个神经元）。用KCI和2-（三甲基氨基）N-（2，6-二甲基苯基）-乙酰胺（QX-314）微电极的振幅达到36.3 +/- 5.2 mV，持续12.5 +/- 6.5 s，反转电位为-31.3 +/- 2.5 mV在这些记录程序下，发作放电幅度为41.5 +/- 5.0 mV，逆转电位为-24.0 +/- 7.0 mV（n = 4个神经元）。单用高甲基-D-天冬氨酸（NMDA）受体拮抗剂3，3-（2-羧基-哌嗪-4-基）-丙-1-膦酸酯（10 μ M，n = 5个神经元）或与非NMDA受体拮抗剂6-氰基-7-硝基-喹喔啉-2，3-二酮（10 μ M，n = 4个神经元）合用，可消除发作性放电，但不影响LLD。用γ-氨基丁酸-A（GABA（A））受体拮抗剂甲碘荷包牡丹碱（BMI，10 μ M，a = 6个神经元）或μ-阿片受体激动剂（D-Ala 2-N-Me-Phe，Glyol）脑啡肽（DAGO，10 μ M，n = 2个神经元）阻断LLD。应用BMI（n = 4个神经元）或DAGO（n = 2个神经元）控制介质，消除了LLD和发作放电，但揭示了一种新型的癫痫样去极化，持续3.5 +/- 1.2 s，每5.2 +/- 2.6 a（n = 6个神经元）发生一次。我们的数据表明，4AP诱导大鼠内嗅皮层的同步，GABA介导的电位，这是在启动NMDA依赖性，发作性放电。此外，我们目前的证据表明，GABA介导的电位在维持和终止这些长期的癫痫样事件中发挥了积极的作用。
Participation of GABA,mediated inhibition In ictallike discharges in the rat entorhinal cortex. J. Neurophysiol. 79: 352-360, 1998. The spontaneous, synchronous activity induced by 4-aminopyridine (4AP, 50 mu M) in the adult rat entorhinal cortex was analyzed with simultaneous held potential and intracellular recordings in an in vitro slice preparation. Four-AP induced isolated negative-going field potentials (interval of occurrence = 27.6 +/- 9.9) (SD) s;( a = 27 slices) that corresponded to intracellular long-lasting depolarizations (LLDs), and ictallike epileptiform discharges (interval of occurrence = 10.4 +/- 5.7 min; n = 27 slices) that were initiated by the negative field potentials. LLDs recorded with K-acetate-filled microelectrodes triggered few action potentials of variable amplitude and had a duration of 1.7 +/- 0.8 s (n = 26 neurons), a peak amplitude of 11.8 +/- 5.0 mV (a = 26 neurons) and a reversal potential of -66.2 +/- 3.9 mV(n = 17 neurons). The ictal discharges studied with K-acetate microelectrodes consisted of prolonged depolarizations (duration = 72.9 +/- 44.3 s; peak amplitude = 29.2 +/- 11.4 mV; n = 25 neurons) with action-potential firing during both the tonic and the clonic phase. These depolarizations had a reversal potential of -45.3 +/- 3.8 mV (n = 4 neurons). Intracellular Cl-diffusion from KCl-filled microelectrodes made both LLDs and ictal depolarizations increase in amplitude (30.5 +/- 8.2 mV, n = 8 and 41.8 +/- 9.8 mV, n = 6 neurons, respectively). LLDs recorded with KCI and 2-(trimethyl-amino)N-(2,6-dimethylphenyl)-acetamide (QX-314) microelectrodes reached an amplitude of 36.3 +/- 5.2 mV, lasted 12.5 +/- 6.5 s, and had a reversal potential of -31.3 +/- 2.5 mV (a = 4 neurons); under these recording procedures the ictal discharge amplitude was 41.5 +/- 5.0 mV and the reversal potential -24.0 +/- 7.0 mV (n = 4 neurons). The hi-methyl-D-aspartate (NMDA) receptor antagonist 3,3-(2-carboxy-piperazine-4-yl)-pro-pyl-l-phosphonate (10 mu M, n = 5 neurons) alone or concomitant with the nonNMDA receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (10 mu M, n = 4 neurons) abolished ictal discharges,without influencing LLDs. LLDs were blocked by the gamma-aminobutyric acid-A (GABA(A)) receptor antagonist bicuculline methiodide (BMI, 10 mu M, a = 6 neurons) or the mu-opioid receptor agonist (D-Ala2-N-Me-Phe, Glyol) enkephalin (DAGO, 10 mu M, n = 2 neurons). Application of BMI (n = 4 neurons) or DAGO (n = 2 neurons) to control the medium abolished LLDs and ictal discharges but disclosed a novel type of epileptiform depolarization that lasted 3.5 +/- 1.2 s and occurred every 5.2 +/- 2.6 a (n = 6 neurons). Our data indicate that 4AP induces in the rat entorhinal cortex a synchronous, GABA-mediated potential that is instrumental in initiating NMDA-dependent, ictal discharges. Moreover we present evidence for an active role played by GABAA-mediated potentials in the maintenance and termination of these prolonged epileptiform events.