Abstract
Midazolam (MDZ), a benzodiazepine analogue, that is clinically used to induce sedation, relieve anxiety, and to impair memory of preoperative events has some unique actions. to explore unknown effects of MDZ on presynaptic GABA release, have not been studied. Thus we examined the effects of MDZ on GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in layer V pyramidal neurons in somatosensory cortex by using whole-cell patch-clamp technique for 2-3 weeks-old rat brain slices. MDZ increases the frequency of GABAergic mIPSC via insertion of α7 nicotinic acetylcholine receptors (nAChRs) at presynaptic GABAergic terminals. MDZ also increased the number of α-bungarotoxin-bound boutons as revealed by confocal imaging. To elucidate the mechanism of nAChR translocation, we examined whether PKC are involved in the action of MDZ by using PKC inhibitors. Bath application of the cell-permeable and specific PKC inhibitor calphostin C (1 μM) for 20 min did not change the mIPSC frequency but blocked its increments by MDZ. Another PKC inhibitor, bisindolylmaleimide (5 μM), gave similar results. Thus, PKC activity is essential for the effect of MDZ. [Jpn J Physiol 55 Suppl:S142 (2005)]
