Arai A, Lynch G
Department of Psychiatry and Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA 92697, USA.
Brain Res. 1998 Jul 20;799(2):235-42. doi: 10.1016/s0006-8993(98)00447-8.
In patches excised from CA1 pyramidal cells, peak amplitudes of currents evoked by brief glutamate pulses grew progressively smaller over a series of high-frequency pulses. This decline was eliminated by cyclothiazide, a drug previously shown to block AMPA receptor desensitization. In hippocampal slices, synaptically evoked bursts exhibited an increase from the first to the second response, presumably due to facilitation of transmitter release, but the subsequent responses gradually declined in amplitude. Cyclothiazide attenuated or reversed this decline; after normalization to the first response, the amplitudes of the later responses to a 50 Hz series of afferent stimulation were increased by 20-25% in regular recording medium and by as much as 40% when transmitter release was enhanced in a high-calcium medium. The effect of cyclothiazide was greatly diminished when the stimulation frequency was reduced to 33 or 25 Hz. Comparable results were obtained in slices in which NMDA, GABAA, and GABAB receptors were blocked. The ampakine drug CX516 which has only a minor influence on desensitization kinetics did not differentially facilitate the later responses to high-frequency afferent stimulation. These results suggest that the desensitization of AMPA receptors contributes importantly to synaptic activity when afferents are repetitively activated at high-frequency.
在从CA1锥体细胞切下的膜片中，短暂谷氨酸脉冲诱发的电流峰值幅度在一系列高频脉冲作用下逐渐变小。这种下降可被环噻嗪消除，环噻嗪是一种先前已证明可阻断AMPA受体脱敏的药物。在海马切片中，突触诱发的阵发放电从第一次反应到第二次反应表现出增加，这可能是由于递质释放的易化作用，但随后的反应幅度逐渐下降。环噻嗪减弱或逆转了这种下降；在以第一次反应为标准进行归一化后，在正常记录介质中，对50Hz传入刺激序列的后续反应幅度增加了20 - 25%，而在高钙介质中增强递质释放时，增加幅度高达40%。当刺激频率降至33Hz或25Hz时，环噻嗪的作用大大减弱。在NMDA、GABAA和GABAB受体被阻断的切片中也获得了类似结果。对脱敏动力学只有轻微影响的安帕金药物CX516并没有对高频传入刺激的后续反应产生差异性的易化作用。这些结果表明，当传入神经以高频重复激活时，AMPA受体的脱敏对突触活动有重要作用。
