Franceschetti S, Hamon B, Heinemann U
Brain Res. 1986 Oct 29;386(1-2):1-11. doi: 10.1016/0006-8993(86)90135-6.
The effects of valproate (VPA) on neuronal excitability and on changes in extracellular potassium ([K+]o) and calcium ([Ca2+]o) were investigated with ion selective-reference electrode pairs in area CA1 of rat hippocampal slices. Field potential responses to single ortho- and antidromic stimuli were unaltered by VPA (1-5 mM). The afferent volley evoked in the Schaffer-commissural fibers was also unaffected. In contrast, VPA (1 mM) depressed frequency potentiation and paired pulse facilitation markedly. Decreases in [Ca2+]o induced either by repetitive stimulation or by application of the excitatory amino acids N-methyl-D-aspartate and quisqualate were reduced, and the latter results suggest that VPA interferes with postsynaptic Ca2+ entry. When synaptic transmission was blocked by lowering [Ca2+]o (0.2 mM) and elevating [Mg2+]o (7 mM), prolonged afterdischarges elicited by antidromic stimulation were blocked by VPA. VPA also suppressed the spontaneous epileptiform activity seen when [Ca2+]o was lowered to 0.2 mM, without elevating [Mg2+]o. The amplitudes of the rises in [K+]o induced by repetitive orthodromic stimulation were only slightly depressed and those elicited by antidromic stimulation were generally unaltered by VPA, as were laminar profiles of stimulus-evoked [K+]o signals. These results indicate that VPA has membrane actions in addition to known effects on excitatory and inhibitory transmitter pools.
利用离子选择性-参比电极对，在大鼠海马切片CA1区研究了丙戊酸盐（VPA）对神经元兴奋性以及细胞外钾离子（[K+]o）和钙离子（[Ca2+]o）变化的影响。VPA（1-5 mM）未改变对单个正向和逆向刺激的场电位反应。在Schaffer-连合纤维中诱发的传入冲动也未受影响。相反，VPA（1 mM）显著抑制频率增强和双脉冲易化。重复性刺激或应用兴奋性氨基酸N-甲基-D-天冬氨酸和quisqualate所诱导的[Ca2+]o降低有所减少，后一结果提示VPA干扰突触后Ca2+内流。当通过降低[Ca2+]o（0.2 mM）和升高[Mg2+]o（7 mM）阻断突触传递时，VPA可阻断逆向刺激所诱发的延长的后放电。VPA还可抑制在不升高[Mg2+]o的情况下将[Ca2+]o降至0.2 mM时所出现的自发性癫痫样活动。重复性正向刺激所诱导的[K+]o升高幅度仅略有降低，而逆向刺激所诱发的[K+]o升高幅度通常未受VPA影响，刺激诱发的[K+]o信号的层状分布也是如此。这些结果表明，VPA除了对兴奋性和抑制性递质池有已知作用外，还具有膜作用。
