Avoli M, Methot M, Kawasaki H
Cell Biology of Excitable Tissue Research Group, Montreal Neurological Institute and Departments of Neurology & Neurosurgery, and of Physiology, McGill University, Montreal, QC, H3A 2B4, Canada.
Eur J Neurosci. 1998 Aug;10(8):2714-22. doi: 10.1046/j.1460-9568.1998.00275.x.
Intracellular recordings from CA3 pyramidal cells of rat hippocampus in a slice preparation revealed the occurrence of interictal epileptiform discharges and synchronous GABA-mediated potentials during application of 4-aminopyridine (4AP, 50 micrometer). The synchronous GABA-mediated potential consisted of a sequence of early hyperpolarization, long-lasting depolarization (LLD), and late hyperpolarization. Action potentials of variable amplitude occurred at the peak of the early hyperpolarization and during the LLD rising phase (48 of 64 cells); they were not prevented by membrane hyperpolarization and displayed inflections that were reminiscent of the initial segment-somatodendritic (IS-SD) fractionation. Interictal discharges were blocked by excitatory amino acid receptor antagonists, while both GABA-mediated potentials and action potentials of variable amplitude continued to occur (n = 10). The latter events were still recorded in the presence of the GABAB receptor antagonist CGP-35348 (0.5-1 mm, n = 4), but were abolished by the GABAA receptor antagonist bicuculline methiodide (BMI, 10 micrometer, n = 5). Localized application of BMI (20 micrometer, n = 6) or tetrodotoxin (TTX, 5 micrometer, n = 3) to the CA1 stratum radiatum blocked the variable amplitude action potentials; these effects were not seen when BMI (n = 4) or TTX (n = 4) were applied to the CA3 stratum radiatum, although both procedures made LLDs disappear. Our findings indicate that action potentials of variable amplitude recorded from CA3 pyramidal cells in the 4AP model are generated at or near the terminal region of the Schaffer collaterals and that they represent TTX-sensitive ectopic events. These action potentials are generated at this site by a BMI-sensitive (and thus GABAA-mediated) mechanism. We propose that the ectopic action potentials reflect an increased excitability of axon terminals that is presumably caused by [K+]o elevations associated with the 4AP-induced synchronous GABA-mediated potential.
在脑片制备中对大鼠海马CA3锥体细胞进行细胞内记录,结果显示在应用4 - 氨基吡啶(4AP,50微摩尔)期间出现了发作间期癫痫样放电以及同步的GABA介导电位。同步的GABA介导电位由一系列早期超极化、持久去极化(LLD)和晚期超极化组成。在早期超极化峰值和LLD上升期(64个细胞中的48个)出现了幅度可变的动作电位;它们不受膜超极化的阻止,并且显示出类似于起始段 - 树突体(IS - SD)分离的转折。发作间期放电被兴奋性氨基酸受体拮抗剂阻断,而GABA介导电位和幅度可变的动作电位仍继续出现(n = 10)。在存在GABAB受体拮抗剂CGP - 35348(0.5 - 1毫米,n = 4)的情况下仍记录到后一种事件,但被GABAA受体拮抗剂荷包牡丹碱甲碘化物(BMI,10微摩尔,n = 5)消除。将BMI(20微摩尔,n = 6)或河豚毒素(TTX,5微摩尔,n = 3)局部应用于CA1辐射层可阻断幅度可变的动作电位;当将BMI(n = 4)或TTX(n = 4)应用于CA3辐射层时未观察到这些效应,尽管这两种操作都会使LLD消失。我们的研究结果表明,在4AP模型中从CA3锥体细胞记录到的幅度可变的动作电位是在Schaffer侧支终末区域或其附近产生的,并且它们代表对TTX敏感的异位事件。这些动作电位在此部位由BMI敏感(因此是GABAA介导)的机制产生。我们提出,异位动作电位反映了轴突终末兴奋性的增加,这可能是由与4AP诱导的同步GABA介导电位相关的细胞外钾离子浓度升高引起的。