title: Differential effects of midazolam on inhibitory postsynaptic currents in CA1 pyramidal cells and dentate gyrus granule cells of rat hippocampal slices.
abstract: To examine regional differences of synaptic transmission, the effects of midazolam were observed on inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal cells (CA1-PCs) and dentate gyrus granule cells (DG-GCs) in rat hippocampal slices. Midazolam is one of the most popular benzodiazepines. The monosynaptic IPSCs in the CA1-PCs and DG-GCs were evoked by electrical stimulation of GABAergic interneurons and recorded by whole cell patch-clamp techniques. The effects of specific concentrations of midazolam (0.3, 1, 10 and 75 microM) on the IPSCs in CA1-PCs and DG-GCs were examined at particular membrane potentials (20 mV steps, from -120 to +40 mV). In all midazolam concentrations tested, the conductance of the IPSCs was significantly larger than that in control and was increased by increasing the concentration of midazolam in CA1-PCs (normalized conductance, 0.3 microM, 121%; 1 microM, 125%; 10 microM, 147%; 75 microM, 147%). However, midazolam did not significantly change the conductance of the IPSCs in DG-GCs (normalized conductance, 0.3 microM, 92%; 1 microM, 92%; 10 microM, 91%; 75 microM, 115%). The normalized conductance was significantly different between the CA1-PCs and DG-GCs in 1 and 10 microM midazolam. The results strongly suggest that the differential effects of midazolam on IPSCs in CA1-PCs and DG-GCs could be, at least in part, due to the different sensitivity to midazolam of the GABA(A) receptor subtypes.
authors.affiliation: Department of Physiology, Sapporo Medical University School of Medicine, South 1, West 17, Chuo-ku, Sapporo 060-8556, Japan. suguruk@sapmed.ac.jp
authors.forename: Suguru
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujito
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Matsuyama
authors.forename: Mamoru
authors.initials: M
authors.lastname: Aoki
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008874:Midazolam / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D008874:Midazolam