抄録
Midazolam (MDZ), a benzodiazepine (BZD) analogue, is clinically used to induce sedation, relieve anxiety, and to impair memory of preoperative events. BZD act at mainly postsynaptic GABAA receptors and enhance the action of inhibitory transmitter GABA. However, 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. The mIPSCs were significantly increased in frequency by 0.1-1 μM MDZ. However, other BZD analogues such as diazepam (0.5 μM) and zolpidem (0.5 μM) did not change the mIPSCs frequency, suggesting that MDZ might enhance the presynaptic GABA release via some mechanism other than GABAA receptor activation. The MDZ-induced incremental effect of mIPSCs frequency was blocked by α7 nicotinic ACh receptor (nAChR) blocker methyllycaconitine, but not by α4β2 nAChR blocker dihydro-β-erythtroidine. Although nicotine alone fail to increase the mIPSCs frequency, pretreatment with MDZ enhanced the nicotine-induced GABA release. These results indicate that MDZ enhanced translocation of nAChR over the membrane surface, hence endogenous ACh increased the release of GABA via α7 nAChR on presynaptic nerve terminal. [Jpn J Physiol 54 Suppl:S146 (2004)]
