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首页> 外文期刊>Journal of Neurophysiology >2-Deoxy-D-glucose reduces epileptiform activity by presynaptic mechanisms
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2-Deoxy-D-glucose reduces epileptiform activity by presynaptic mechanisms

机译：2-脱氧-D-葡萄糖通过突触前机制降低癫痫型活性

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摘要

2-Deoxy-D-glucose (2DG), a glucose analog that inhibits glycolysis, has acute and chronic antiepileptic effects. We evaluated 2DG's acute effects on synaptic and membrane properties of CA3 pyramidal neurons in vitro. 2DG (10 mM) had no effects on spontaneously occurring postsynaptic currents (PSCs) in 3.5 mM extracellular potassium concentration ([K+](o)). In 7.5 mM [K+](o), 2DG significantly reduced the frequency of epileptiform bursting and the charge carried by postsynaptic currents (PSCs) with a greater effect on inward excitatory compared with outward inhibitory charge (71% vs. 40%). In 7.5 mM [K+](o) and bicuculline, 2DG reduced significantly the excitatory charge by 67% and decreased the frequency but not amplitude of excitatory PSCs between bursts. In 7.5 mM [K+](o), 2DG reduced pharmacologically isolated inhibitory PSC frequency without a change in amplitude. The frequency but not amplitude of inward miniature PSCs was reduced when 2DG was applied in 7.5 mM [K+](o) before bath application of TTX, but there was no effect when 2DG was applied after TTX, indicating a use-dependent uptake of 2DG was required for its actions at a presynaptic locus. 2DG did not alter membrane properties of CA3 neurons except for reducing the slow afterhyperpolarization in 3.5 but not 7.5 mM [K+](o). The reduction in frequency of spontaneous and inward miniature PSCs in elevated [K+](o) indicates a presynaptic mechanism of action. 2DG effects required use-dependent uptake and suggest an important role for glycolysis in neuronal metabolism and energetics in states of high neural activity as occur during abnormal network synchronization and seizures.
机译：2-脱氧-D-葡萄糖（2DG），抑制糖酵解的葡萄糖类似物，具有急性和慢性抗癫痫作用。我们在体外评估了对Ca3金字塔神经元突触和膜特性的2Dg急性作用。 2dg（10 mm）对3.5mM细胞外钾浓度（[k +]（O））中的3.5mM细胞内浓度（pscs）没有作用。在7.5mm [k +]（O）中，2dg显着降低了癫痫型爆破的频率和突触后电流（pscs）的电荷，与向外抑制电荷（71％vs.40％）相比具有更大的对内兴奋剂的影响。在7.5mm [k +]（O）和Biculline中，2dg显着降低了兴奋性的兴奋性，并降低了爆发之间的频率但不升级的兴奋性PSC。在7.5mm [k +]（O）中，2dg减少了药理学上分离的抑制性psc频率，而不会变化幅度。当在7.5mm [k +]（o）施用TTX之前将2dg施用2dg，但在TTX施加2DG时，当TTX施加2DG时，频率但不幅度的频率降低，但是在TTX后施加2DG，表示使用依赖于2DG的使用依赖性摄取在突触前轨的行动是必需的。除了在3.5中减少3.5中的缓慢后渗透性之外，2dg没有改变Ca3神经元的膜性能，但不是7.5mm [k +]（o）。在升高的[k +]（O）中的自发和向内微型PSC频率的频率降低表明了突触前的作用机制。 2DG效应所需的使用依赖性摄取，并表明在异常网络同步和癫痫发作期间发生高神经活动状态的神经元代谢和能量学中的糖酵解的重要作用。

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