Sato Y, Fujito Y, Aoki M
Department of Physiology, Sapporo Medical University School of Medicine, Japan.
Brain Res. 1997 Oct 31;773(1-2):98-107. doi: 10.1016/s0006-8993(97)00920-7.
The effects of midazolam, one of the most popular benzodiazepines, on synaptic transmissions were compared with intracellular recordings between CA1 pyramidal cells (CA1-PCs) and dentate gyrus granule cells (DG-GCs) in rat hippocampal slices. First, we studied the effects of midazolam on orthodromically evoked spikes, membrane properties and synaptic potentials. Secondly, the effects of a GABA(A) receptor agonist, muscimol, were examined on membrane properties to determine whether or not the densities of GABA(A) receptors are different between CA1-PCs and DG-GCs. Midazolam (75 microM) markedly depressed orthodromically evoked spikes in CA1-PCs, compared with those in DG-GCs. A GABA(A) receptor antagonist, bicuculline (10 microM), almost completely antagonized the depressant effects of midazolam on spike generation in CA1-PCs, whereas it had little effect on midazolam in dentate gyrus granule cells. Midazolam produced either depolarizing or hyperpolarizing effects on resting membrane potentials (Vm) with an input resistance decrease in CA1-PCs, whereas it produced depolarized Vm in DG-GCs. Midazolam significantly increased the amplitude of monosynaptic inhibitory postsynaptic potentials in CA1-PCs, whereas midazolam slightly decreased these in DG-GCs. Midazolam significantly decreased the amplitude of excitatory postsynaptic potentials both in CA1-PCs and DG-GCs. Muscimol (100 microM) produced either depolarizing or hyperpolarizing effects on Vm with an input resistance decrease in CA1-PCs, and it depolarized Vm with an input resistance decrease in DG-GCs. These results demonstrate that midazolam has differential effects on excitatory and inhibitory synaptic transmissions in hippocampal neurons. The mechanism of this difference could be partly due to the different types of GABA(A) receptors between CA1-PCs and DG-GCs.
将最常用的苯二氮䓬类药物之一咪达唑仑对突触传递的影响，与大鼠海马脑片CA1锥体细胞（CA1-PCs）和齿状回颗粒细胞（DG-GCs）之间的细胞内记录进行了比较。首先，我们研究了咪达唑仑对顺向诱发动作电位、膜特性和突触电位的影响。其次，研究了γ-氨基丁酸A（GABA(A)）受体激动剂蝇蕈醇对膜特性的影响，以确定CA1-PCs和DG-GCs之间GABA(A)受体的密度是否不同。与DG-GCs相比，咪达唑仑（75微摩尔）显著抑制CA1-PCs中的顺向诱发动作电位。GABA(A)受体拮抗剂荷包牡丹碱（10微摩尔）几乎完全拮抗了咪达唑仑对CA1-PCs中动作电位产生的抑制作用，而对齿状回颗粒细胞中的咪达唑仑作用很小。咪达唑仑对CA1-PCs的静息膜电位（Vm）产生去极化或超极化作用，同时输入电阻降低，而在DG-GCs中则产生去极化的Vm。咪达唑仑显著增加CA1-PCs中单个突触抑制性突触后电位的幅度，而在DG-GCs中则略有降低。咪达唑仑显著降低CA1-PCs和DG-GCs中兴奋性突触后电位的幅度。蝇蕈醇（100微摩尔）对CA1-PCs的Vm产生去极化或超极化作用，同时输入电阻降低，对DG-GCs的Vm产生去极化作用，同时输入电阻降低。这些结果表明，咪达唑仑对海马神经元的兴奋性和抑制性突触传递有不同的影响。这种差异的机制可能部分归因于CA1-PCs和DG-GCs之间不同类型的GABA(A)受体。
