Synaptic excitation mediated by AMPA receptors in rat cerebellar slices is selectively enhanced by aniracetam and cyclothiazide
Synaptic excitation mediated by AMPA receptors in rat cerebellar slices is selectively enhanced by aniracetam and cyclothiazide
复制标题
阿尼西坦和环噻嗪选择性增强大鼠小脑切片中 AMPA 受体介导的突触兴奋
DOI：
10.1007/bf01694543
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发表时间：
1995
影响因子：
4.4
通讯作者：
J. Garthwaite
中科院分区：
文献类型：
--
作者：
Andrew R. Boxall;J. Garthwaite
AMPA受体介导中枢神经系统中快速的谷氨酸能突触传递。相关突触后电流的时间过程主要由谷氨酸结合和受体脱敏的动力学决定。阿尼西坦和环噻嗪是能够选择性地阻止AMPA受体脱敏的药物。为了研究脱敏与小脑快速突触传递的相关性，我们使用脂隙记录技术测试了这些化合物对ampa诱导的去极化和突触后电位的影响。阿尼西坦（1 μM-5 mM）和环噻嗪（1 μM-500 μM）均能增强AMPA （1 μM-500 μM）对浦肯野细胞的去极化作用，且呈浓度依赖性。在测试的最高浓度下，比对照分别增加了约600%和800%。阿尼西坦还以浓度依赖性的方式增加了平行纤维-浦肯野细胞和苔藓纤维-颗粒细胞通路的诱发突触电位的振幅，其中最高浓度的电位分别提高了约60%和75%。这些数据表明，在小脑的两个不同的突触上，AMPA受体脱敏发生在生理上，并且可能有助于快速突触电流的形成。
AMPA receptors mediate fast, glutamatergic synaptic transmission in the central nervous system. The time-course of the associated postsynaptic current has been suggested to be determined principally by the kinetics of glutamate binding and receptor desensitization. Aniracetam and cyclothiazide are drugs capable of selectively preventing desensitization of the AMPA receptor. To investigate the relevance of desensitization to fast synaptic transmission in the cerebellum we have tested these compounds against AMPA-induced depolarizations and postsynaptic potentials using the grease-gap recording technique. Aniracetam (1 μM-5 mM) and cyclothiazide (1 μM-500 μM) both enhanced the depolarising action of AMPA (1 μM) on Purkinje cells in a concentration-dependent manner. At the highest concentrations tested, the increases over controls were approximately 600% and 800% respectively. Aniracetam also increased, in a concentration-dependent manner, the amplitude of the evoked synaptic potentials of both parallel fibre-Purkinje cell and mossy fibre-granule cell pathways, with the highest concentrations tested enhancing the potentials by approximately 60% and 75% respectively. These data suggest that, at two different synapses in the cerebellum, AMPA receptor desensitization occurs physiologically and is likely to contribute to the shape of fast synaptic currents.
影响因子：
56.9
作者：
CLEMENTS, JD;LESTER, RAJ;WESTBROOK, GL
通讯作者：
WESTBROOK, GL