Adenosine A1 receptor-mediated presynaptic inhibition at the calyx of Held of immature rats
Adenosine A1 receptor-mediated presynaptic inhibition at the calyx of Held of immature rats
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DOI：
10.1113/jphysiol.2003.048371
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发表时间：
2003-12-01
影响因子：
5.5
通讯作者：
Takahashi, T
中科院分区：
文献类型：
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作者：
Kimura, M;Saitoh, N;Takahashi, T
在5- 7日龄（P5-7）大鼠脑干切片的Held突触的萼部，腺苷或腺苷（A（1））I型受体激动剂N-6-环戊基腺苷（CPA）抑制兴奋性突触后电流（EPSCs），但不影响微小EPSCs的振幅。A（1）受体拮抗剂8-环戊基茶碱（CPT）对低频诱发的EPSC振幅无影响，但可显著降低10 Hz重复刺激引起的突触抑制幅度，提示内源性腺苷参与了递质释放的调节。腺苷抑制突触前Ca ~（2+）电流（I-pCa），但对突触前K ~+电流无影响。在突触前和突触后同时记录时，IpCa诱发EPSC时，腺苷诱导的IpCa抑制的幅度充分解释了EPSC的抑制，表明突触前Ca ~（2+）通道是A（1）受体的主要靶点。而N-型钙通道阻滞剂ω-芋螺毒素衰减EPSCs，它对腺苷诱导的抑制EPSCs的幅度没有影响。在出生后的发育过程中，与肾盏末端A（1）受体免疫反应性的减少平行，腺苷的抑制作用减弱。我们的结论是，突触前A（1）受体在未成熟的萼的Held突触发挥调节作用，在高频率传输的递质释放，通过抑制多种类型的突触前Ca 2+通道。
At the calyx of Held synapse in brainstem slices of 5- to 7-day-old (P5-7) rats, adenosine, or the type I 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 Ca2+ currents (I-pCa) 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 Ca2+ channel is the main target of A(1) receptors. Whereas the N-type Ca2+ 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 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 Ca2+ channels.