Clark K A, Randall A D, Collingridge G L
Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, UK.
Exp Brain Res. 1994;101(2):272-8. doi: 10.1007/BF00228747.
Paired-pulse facilitation of excitatory synaptic transmission was investigated in the CA1 region of rat hippocampal slices using whole-cell patch-clamp recording. To optimise the measurement of excitatory synaptic transmission, gamma-amino-butyric acid (GABA)-mediated synaptic inhibition was eliminated using both GABAA and GABAB antagonists. Pure alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic currents (EPSCs) were then isolated pharmacologically. Paired-pulse facilitation of either AMPA or NMDA receptor-mediated EPSCs (EPSCA and EPSCN, respectively) was investigated using two stimuli of identical strength delivered at intervals of between 25 and 1000 ms. The paired-pulse facilitation profiles of both EPSCA and EPSCN were similar. Paired-pulse facilitation of EPSCA was independent of holding potential. In contrast paired-pulse facilitation of EPSCN was markedly voltage-dependent; maximum facilitation was recorded at hyperpolarised membrane potentials. At positive membrane potentials there was little or no paired-pulse facilitation and, in most neurones, paired-pulse depression was observed. Voltage-dependence of paired-pulse facilitation of EPSCN was similar in the presence of nominal absence of Mg2+ in the bathing medium, and was unaffected by extensive dialysis of neurones with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). These data are consistent with a presynaptic locus for paired-pulse facilitation of EPSCA. However, paired-pulse facilitation of EPSCN involves postsynaptic factors.
采用全细胞膜片钳记录技术，在大鼠海马脑片的CA1区研究兴奋性突触传递的双脉冲易化现象。为优化兴奋性突触传递的测量，使用GABAA和GABAB拮抗剂消除γ-氨基丁酸（GABA）介导的突触抑制。然后通过药理学方法分离出纯α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）或N-甲基-D-天冬氨酸（NMDA）受体介导的兴奋性突触后电流（EPSC）。使用强度相同、间隔时间在25至1000毫秒之间的两个刺激，研究AMPA或NMDA受体介导的EPSC（分别为EPSCA和EPSCN）的双脉冲易化现象。EPSCA和EPSCN的双脉冲易化曲线相似。EPSCA的双脉冲易化与钳制电位无关。相比之下，EPSCN的双脉冲易化明显依赖电压；在超极化膜电位时记录到最大易化。在正膜电位时，几乎没有或没有双脉冲易化，并且在大多数神经元中观察到双脉冲抑制。在浴液中名义上不存在或存在Mg2+的情况下，EPSCN双脉冲易化的电压依赖性相似，并且用1,2-双（2-氨基苯氧基）乙烷-N,N,N',N'-四乙酸（BAPTA）对神经元进行广泛透析对其没有影响。这些数据与EPSCA双脉冲易化的突触前位点一致。然而，EPSCN的双脉冲易化涉及突触后因素。
