Poncer J C, Dürr R, Gähwiler B H, Thompson S M
Brain Research Institute, University of Zurich, Switzerland.
Neuropharmacology. 1996;35(9-10):1169-79. doi: 10.1016/s0028-3908(96)00055-x.
The effects of the benzodiazepine agonist midazolam on GABAA receptor-mediated inhibition were investigated in area CA3 of hippocampal slice cultures. Midazolam (100 nM) increased the decay time constant (tau OFF) of miniature inhibitory postsynaptic currents (mIPSCs) recorded from pyramidal cells by approximately 40%, but did not significantly affect their activation rate or amplitude, consistent with saturation of postsynaptic GABAA receptors by a quantum of GABA. Non-stationary variance analysis of mIPSCs revealed that the unitary conductance of synaptic GABAA channels (approximately 31 pS) was unaffected by midazolam. Midazolam increased not only the tau OFF (51%), but also the amplitude (23%) of unitary IPSPs, recorded from pairs of monosynaptically connected inhibitory and pyramidal cells. Simulation of unitary IPSPs indicated that the increased amplitude was primarily due to the slow time constant of pyramidal cells. Finally, the mean amplitude, tau OFF, and single-channel conductance of mIPSCs recorded in cultures chronically exposed to midazolam (0.1-10 microM) for 2 weeks were not different from control mIPSCs, nor was their response to midazolam. We conclude that benzodiazepines increase synaptic GABAA channel open time, as described previously, and that this results in an increase in both the amplitude and duration of IPSPs in pyramidal cells.
在海马切片培养物的CA3区研究了苯二氮䓬类激动剂咪达唑仑对GABAA受体介导的抑制作用。咪达唑仑（100 nM）使从锥体细胞记录的微小抑制性突触后电流（mIPSCs）的衰减时间常数（tau OFF）增加了约40%，但对其激活率或幅度没有显著影响，这与一个GABA量子使突触后GABAA受体饱和一致。对mIPSCs的非平稳方差分析表明，突触GABAA通道的单位电导（约31 pS）不受咪达唑仑影响。咪达唑仑不仅增加了从单突触连接的抑制性和锥体细胞对记录的单位IPSPs的tau OFF（51%），还增加了其幅度（23%）。单位IPSPs的模拟表明，幅度增加主要是由于锥体细胞的时间常数较慢。最后，在长期暴露于咪达唑仑（0.1 - 10 microM）2周的培养物中记录的mIPSCs的平均幅度、tau OFF和单通道电导与对照mIPSCs没有差异，它们对咪达唑仑的反应也没有差异。我们得出结论，如先前所述，苯二氮䓬类药物增加突触GABAA通道的开放时间，这导致锥体细胞中IPSPs的幅度和持续时间增加。
