Differential effects of midazolam on inhibitory postsynaptic currents in CA1 pyramidal cells and dentate gyrus granule cells of rat hippocampal slices.

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.