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 μM) 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 μM, 121%; 1 μM, 125%; 10 μM, 147%; 75 μM, 147%). However, midazolam did not significantly change the conductance of the IPSCs in DG-GCs (normalized conductance, 0.3 μM, 92%; 1 μM, 92%; 10 μM, 91%; 75 μM, 115%). The normalized conductance was significantly different between the CA1-PCs and DG-GCs in 1 and 10 μM 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.
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