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):230-4. doi: 10.1016/s0006-8993(98)00446-6.
Relationships between the kinetic properties of AMPA receptors and the decay phase of fast excitatory transmission were investigated using modulatory drugs. The benzothiadiazide compound cyclothiazide blocked receptor desensitization in patches excised from hippocampus but had only a weak influence on receptor deactivation, i.e., on the decay of responses produced by a 1-ms pulse of glutamate. The ampakine drug CX516 (BDP-12) produced an opposite pattern of effects: a fourfold slowing of deactivation with little change in desensitization. A structurally related drug (CX554 or BDP-20) had prominent effects on both desensitization and deactivation. The halfwidth of field EPSPs measured in the CA1 region of hippocampal slices increased 50-100% in the presence of CX516 or CX554 but by less than 15% at concentrations of cyclothiazide that fully blocked desensitization in patch experiments. These results indicate that receptor deactivation plays a substantially greater role than receptor desensitization in determining the duration of synaptic responses.
使用调节药物研究了AMPA受体的动力学特性与快速兴奋性传递衰减阶段之间的关系。苯并噻二嗪化合物环噻嗪可阻断从海马体分离的膜片中受体的脱敏，但对受体失活的影响较弱，即对1毫秒谷氨酸脉冲产生的反应衰减影响较小。安帕金药物CX516（BDP-12）产生了相反的效应模式：失活减慢四倍，脱敏变化不大。一种结构相关药物（CX554或BDP-20）对脱敏和失活均有显著影响。在海马体切片CA1区测量的场兴奋性突触后电位（fEPSP）半宽度在存在CX516或CX554时增加了50%-100%，但在膜片实验中完全阻断脱敏的环噻嗪浓度下增加不到15%。这些结果表明，在确定突触反应持续时间方面，受体失活比受体脱敏起着更大的作用。
