THE ACTION OF VALPROATE ON SPONTANEOUS EPILEPTIFORM ACTIVITY IN THE ABSENCE OF SYNAPTIC TRANSMISSION AND ON EVOKED CHANGES IN [CA2+]O AND [K+]O IN THE HIPPOCAMPAL SLICE
THE ACTION OF VALPROATE ON SPONTANEOUS EPILEPTIFORM ACTIVITY IN THE ABSENCE OF SYNAPTIC TRANSMISSION AND ON EVOKED CHANGES IN [CA2+]O AND [K+]O IN THE HIPPOCAMPAL SLICE
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DOI：
10.1016/0006-8993(86)90135-6
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发表时间：
1986-10-29
期刊：
影响因子：
2.9
通讯作者：
HEINEMANN, U
中科院分区：
文献类型：
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作者：
FRANCESCHETTI, S;HAMON, B;HEINEMANN, U
采用离子选择参比电极对大鼠海马CA1区观察丙戊酸钠（VPA）对神经元兴奋性和胞外钾（[K+]o）、钙（[Ca2+]o）变化的影响。VPA （1-5 mM）未改变对单正、反负刺激的场电位反应。Schaffer-commissural纤维中引起的传入射击也不受影响。相反，VPA （1 mM）明显抑制频率增强和配对脉冲促进。通过重复刺激或应用兴奋性氨基酸n -甲基- d -天冬氨酸和准质酸诱导的[Ca2+]o的减少减少，后者的结果表明VPA干扰突触后Ca2+进入。当突触传递被VPA阻断时。当[Ca2+]o降低至0.2 mM时，VPA也抑制自发性癫痫样活动，而不升高[Mg2+]o。重复正交刺激引起的[K+]0上升幅度仅轻微下降，反正交刺激引起的[K+]0上升幅度一般不受VPA的影响，刺激引起的[K+]0信号的层流分布也是如此。这些结果表明，除了已知的兴奋性和抑制性递质库作用外，VPA还具有膜作用。
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 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+]0 signals. These results indicate that VPA has membrane actions in addition to known effects on excitatory and inhibitory transmitter pools.