Adenosine A(1) receptor-mediated presynaptic inhibition at the calyx of Held of immature rats.
At the calyx of Held synapse in brainstem slices of 5- to 7-day-old (P5-7) rats, adenosine, or the type 1 adenosine (A1) receptor agonist N6-cyclopentyladenosine (CPA), inhibited excitatory postsynaptic currents (EPSCs) without affecting the amplitude of miniature EPSCs. The A1 receptor antagonist 8-cyclopentyltheophylline (CPT) had no effect on the amplitude of EPSCs evoked at a low frequency, but significantly reduced the magnitude of synaptic depression caused by repetitive stimulation at 10 Hz, suggesting that endogenous adenosine is involved in the regulation of transmitter release. Adenosine inhibited presynaptic Ca(2+) currents (IpCa) recorded directly from calyceal terminals, but had no effect on presynaptic K+ currents. When EPSCs were evoked by IpCa during simultaneous pre- and postsynaptic recordings, the magnitude of the adenosine-induced inhibition of IpCa fully explained that of EPSCs, suggesting that the presynaptic Ca(2+) channel is the main target of A1 receptors. Whereas the N-type Ca(2+) channel blocker omega-conotoxin attenuated EPSCs, it had no effect on the magnitude of adenosine-induced inhibition of EPSCs. During postnatal development, in parallel with a decrease in the A1 receptor immunoreactivity at the calyceal terminal, the inhibitory effect of adenosine became weaker. We conclude that presynaptic A1 receptors at the immature calyx of Held synapse play a regulatory role in transmitter release during high frequency transmission, by inhibiting multiple types of presynaptic Ca(2+) channels.
Kimura
Masahiro
M
Department of Neurophysiology, University of Tokyo Graduate School of Medicine, Tokyo 113-0033, Japan.
Saitoh
Naoto
N
Takahashi
Tomoyuki
T
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001306:Auditory Pathways / Q000737:chemistry / Q000254:growth & development* / Q000502:physiology; D001418:Baclofen / Q000494:pharmacology; D015153:Blotting, Western; D001933:Brain Stem / Q000737:chemistry / Q000254:growth & development* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D058786:GABA-B Receptor Agonists; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D009433:Neural Inhibition / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000032:analysis / Q000235:genetics / Q000502:physiology; D016708:Synaptophysin / Q000032:analysis; D013779:Tetrodotoxin / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D015220:Calcium Channels; D058786:GABA-B Receptor Agonists; D015221:Potassium Channels; D043682:Receptor, Adenosine A1; D017661:Receptors, Presynaptic; D016708:Synaptophysin; C053907:8-cyclopentyl-1,3-dimethylxanthine; C048599:N(6)-cyclopentyladenosine; D013779:Tetrodotoxin; D020866:omega-Conotoxin GVIA; D013806:Theophylline; D001418:Baclofen; D000241:Adenosine; D011188:Potassium; D002118:Calcium