Lambert J D, Fueta Y, Roepstorff A, Andreasen M
PharmaBiotec, Institute of Physiology, University of Aarhus, Denmark.
Epilepsy Res. 1996 Dec;26(1):15-23. doi: 10.1016/s0920-1211(96)00035-6.
In order to determine whether changes in synaptic inhibition are involved in chronic models of epilepsy, it is necessary to understand the factors which determine the kinetics of fast gamma-aminobutyric acid (GABA)ergic inhibition. For this purpose, we analyzed the decaying phase of isolated inhibitory postsynaptic currents (IPSC) in rats CA1 pyramidal cells. Reduction of GABA release (by reducing [Ca2+]o or paired-pulse stimulation) or blockade of GABA uptake (with tiagabine) led to the conclusion that small changes in the amount of GABA available for postsynaptic binding have little effect on the peak amplitude, but have marked effect on the duration of the IPSC. We then studied isolated GABAA receptor-mediated inhibition in area CA1 of the El mouse strain, which is genetically predisposed to epilepsy. Results were compared with the non-epileptogenic mother strain, ddY. Inhibitory postsynaptic potentials (IPSPs) in El mice (IPSPEl) were not significantly different in amplitude of those from ddY mice (IPSPddY). However, the rise-time and duration of IPSPEl were respectively about 25% and 50% shorter than those of IPSPddY. With appropriate pharmacological manipulation of GABA release or uptake, IPSPEl could be made to resemble the IPSPddY and vice versa. It is concluded that the synaptic release of GABA in area CA1 of the El mouse is decreased compared to that of the ddY mouse.
为了确定突触抑制的变化是否与慢性癫痫模型有关，有必要了解决定快速γ-氨基丁酸（GABA）能抑制动力学的因素。为此，我们分析了大鼠CA1锥体细胞中分离的抑制性突触后电流（IPSC）的衰减阶段。GABA释放减少（通过降低细胞外[Ca2+]或配对脉冲刺激）或GABA摄取阻断（用噻加宾）得出的结论是，可用于突触后结合的GABA量的微小变化对峰值幅度影响不大，但对IPSC的持续时间有显著影响。然后，我们研究了易患癫痫的El小鼠品系CA1区中分离的GABAA受体介导的抑制作用。将结果与非致痫性母系品系ddY进行比较。El小鼠的抑制性突触后电位（IPSPEl）的幅度与ddY小鼠的（IPSPddY）没有显著差异。然而，IPSPEl的上升时间和持续时间分别比IPSPddY短约25%和50%。通过对GABA释放或摄取进行适当的药理学操作，IPSPEl可以变得与IPSPddY相似，反之亦然。得出的结论是，与ddY小鼠相比，El小鼠CA1区的GABA突触释放减少。
