抄録
At the calyx of Held, excitatory transmitter L-glutamate inhibits transmitter release. This effect is mediated by mGluRs (Takahashi et al, 1996) and iGluRs, such as AMPARs (Takago et al, 2005) and also possibly by NMDARs at the nerve terminal. We investigated the mechanisms underlying presynaptic inhibitions by AMPARs and NMDARs using whole-cell recordings from presynaptic terminals and postsynaptic cells. Activation of AMPARs inhibited presynaptic Ca2+ currents (IpCa) and attenuated NMDA-EPSCs. The AMPA-induced IpCa inhibition was disinhibited by a strong depolarization and occluded by GTPγS loaded into the terminal. Thus, activation of presynaptic AMPARs inhibits voltage-gated Ca2+ channels via interaction with Gβγ, thereby attenuating glutamate release. Our preliminary data also suggest that glutamate-induced IpCa inhibition can be mediated by NMDARs. Bath application of NMDA inhibited IpCa. Loading of the NMDAR channel blocker MK-801 into the calyx presynaptic terminal, or bath application of NMDAR antagonists abolished this effect. As a result bath-applied NMDA attenuated AMPA-EPSCs. Surprisingly, intraterminal GTPγS did not affect NMDA-induced IpCa inhibition. Thus at the calyx of Held, the G protein-dependent IpCa inhibition by glutamate is mediated by both mGluRs and AMPARs, but not by NMDARs. [J Physiol Sci. 2008;58 Suppl:S17]
