G protein-dependent presynaptic inhibition mediated by AMPA receptors at the calyx of Held.
The alpha-amino-3-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is an ionotropic receptor mediating excitatory synaptic transmission, but it can also interact with intracellular messengers. Here we report that, at the calyx of Held in the rat auditory brainstem, activation of AMPARs induced inward currents in the nerve terminal and inhibited presynaptic Ca2+ currents (I(pCa)), thereby attenuating glutamatergic synaptic transmission. The AMPAR-mediated I(pCa) inhibition was disinhibited by a strong depolarizing pulse and occluded by the nonhydrolyzable GTP analog GTPgammaS loaded into the terminal. We conclude that functional AMPARs are expressed at the calyx of Held nerve terminal and that their activation inhibits voltage-gated Ca2+ channels by an interaction with heterotrimeric GTP-binding proteins (G proteins). Thus, at a central glutamatergic synapse, presynaptic AMPARs have a metabotropic nature and regulate transmitter release by means of G proteins.
Takago
Hideki
H
Department of Neurophysiology, University of Tokyo Graduate School of Medicine, Hongo, Bunkyo, Tokyo 113-0033, Japan.
Nakamura
Yukihiro
Y
Takahashi
Tomoyuki
T
D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem; D019706:Excitatory Postsynaptic Potentials; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000819:agonists* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D015220:Calcium Channels; D018091:Receptors, AMPA; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C012301:domoic acid; D007608:Kainic Acid; D002118:Calcium