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Adenosine A 1 receptor‐mediated presynaptic inhibition at the calyx of Held of immature rats
Author(s) -
Kimura Masahiro,
Saitoh Naoto,
Takahashi Tomoyuki
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2003.048371
Subject(s) - adenosine , excitatory postsynaptic potential , postsynaptic potential , inhibitory postsynaptic potential , adenosine a1 receptor , neurotransmission , postsynaptic current , synapse , agonist , neuroscience , adenosine receptor , chemistry , biology , receptor , medicine , biophysics , endocrinology , biochemistry
At the calyx of Held synapse in brainstem slices of 5‐ to 7‐day‐old (P5–7) rats, adenosine, or the type 1 adenosine (A 1 ) receptor agonist N 6 ‐cyclopentyladenosine (CPA), inhibited excitatory postsynaptic currents (EPSCs) without affecting the amplitude of miniature EPSCs. The A 1 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 ( I pCa ) recorded directly from calyceal terminals, but had no effect on presynaptic K + currents. When EPSCs were evoked by I pCa during simultaneous pre‐ and postsynaptic recordings, the magnitude of the adenosine‐induced inhibition of I pCa fully explained that of EPSCs, suggesting that the presynaptic Ca 2+ channel is the main target of A 1 receptors. Whereas the N‐type Ca 2+ channel blocker ω‐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 A 1 receptor immunoreactivity at the calyceal terminal, the inhibitory effect of adenosine became weaker. We conclude that presynaptic A 1 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.