二氮嗪可阻断大鼠海马神经元中的谷氨酸脱敏并延长兴奋性突触后电流。

Diazoxide blocks glutamate desensitization and prolongs excitatory postsynaptic currents in rat hippocampal neurons.

Yamada K A, Rothman S M

Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110.

J Physiol. 1992 Dec;458:409-23. doi: 10.1113/jphysiol.1992.sp019424.

Abstract

The effects of diazoxide (DZ) on synaptic transmission and upon responses to exogenously applied glutamate agonists were examined in cultured hippocampal neurons. 2. DZ reversibly increased the peak amplitude of evoked excitatory postsynaptic currents (EPSCs) to 150 +/- 100% of control and prolonged the EPSC decay time constant (tau) from 5.9 +/- 1.2 ms to 14 +/- 6.2 ms (240% of control). 3. Peak and steady-state glutamate (Glu) and quisqualate (QA) currents activated by exogenous application were dramatically increased by DZ at concentrations which did not influence N-methyl-D-aspartate (NMDA), kainate (KA), or GABA currents. These effects were rapidly and completely reversible. Active and passive membrane properties were unaffected by DZ. 4. Inhibitory postsynaptic currents (IPSCs) were unaffected by the same DZ concentrations. 5. These experiments indicate that desensitization plays an important role in terminating excitatory transmission between mammalian central neurons. DZ and perhaps related compounds will ultimately help us identify the regions of the AMPA/KA receptor responsible for desensitization.

摘要

在培养的海马神经元中研究了二氮嗪（DZ）对突触传递以及对外源性应用谷氨酸激动剂反应的影响。2. DZ可逆地将诱发的兴奋性突触后电流（EPSCs）的峰值幅度增加至对照的150±100%，并将EPSC衰减时间常数（tau）从5.9±1.2毫秒延长至14±6.2毫秒（对照的240%）。3. 在外源性应用激活的峰值和稳态谷氨酸（Glu）及quisqualate（QA）电流在不影响N-甲基-D-天冬氨酸（NMDA）、海人藻酸（KA）或γ-氨基丁酸（GABA）电流的浓度下被DZ显著增加。这些效应迅速且完全可逆。主动和被动膜特性不受DZ影响。4. 抑制性突触后电流（IPSCs）不受相同DZ浓度的影响。5. 这些实验表明脱敏在终止哺乳动物中枢神经元之间的兴奋性传递中起重要作用。DZ以及可能相关的化合物最终将帮助我们确定负责脱敏的AMPA/KA受体区域。