Boxall A R, Garthwaite J
Neuroscience Research Group, Wellcome Research Laboratories, Kent, England.
Neurochem Res. 1995 May;20(5):605-9. doi: 10.1007/BF01694543.
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 microM-5 mM) and cyclothiazide (1 microM-500 microM) both enhanced the depolarising action of AMPA (1 microM) 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.
AMPA 受体介导中枢神经系统中快速的谷氨酸能突触传递。有研究表明，相关突触后电流的时间进程主要由谷氨酸结合动力学和受体脱敏决定。阿尼西坦和环噻嗪是能够选择性阻止 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，我们使用油脂间隙记录技术，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）均以浓度依赖性方式增强了 AMPA（1 μM）对浦肯野细胞的去极化作用。在测试的最高浓度下，与对照组相比的增加幅度分别约为 600% 和 800%。阿尼西坦还以浓度依赖性方式增加了平行纤维 - 浦肯野细胞和苔藓纤维 - 颗粒细胞通路诱发的突触电位幅度，测试的最高浓度分别使电位增强了约 60% 和 75%。这些数据表明，在小脑的两个不同突触处，AMPA 受体脱敏在生理上会发生，并且可能对快速突触电流的波形产生影响。
