Ryanodine receptors contribute to the induction of nociceptive input-evoked long-term potentiation in the rat spinal cord slice.

Ryanodine receptors contribute to the induction of nociceptive input-evoked long-term potentiation in the rat spinal cord slice.
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Ryanodine 受体有助于诱导大鼠脊髓切片中伤害性输入诱发的长期增强

DOI:
10.1186/1744-8069-6-1
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发表时间:
2010-01-20
期刊:
影响因子:
3.3
通讯作者:
Zhao ZQ
Zhao ZQ
中科院分区:
医学3区
文献类型:
--
作者:
Cheng LZ;Lü N;Zhang YQ;Zhao ZQ

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背景本实验室前期研究表明,在体脊髓内,一氧化氮(NO)参与强直刺激坐骨神经引起的C纤维诱发场电位长时程增强(LTP)。Ryanodine受体(RyR)是NO的下游靶点。本研究进一步探讨了RyR在脊髓痛通路突触可塑性中的作用。ResultsBy means of field potential recordings in the adult male ratin vivo,我们发现RyR拮抗剂降低了强直刺激坐骨神经引起的脊髓背角C纤维诱发反应的LTP。采用脊髓切片制备和浅层背角场电位记录,高频刺激Lissauer束(LT)稳定地诱导场兴奋性突触后电位(fEPSP)的LTP。灌注RyR拮抗剂可阻断LT刺激诱发的脊髓LTP的诱导,而灌注Ins(1,4,5)P3受体(IP3R)拮抗剂对LTP的诱导无明显影响。此外,激活RyRs的咖啡因没有高频刺激诱导的长时程增强的存在下,荷包牡丹碱甲碘化和士的宁。此外,在从浅表背角神经元的膜片钳记录中,RyR的激活导致微型EPSC(mEPSC)的频率大幅增加。免疫组化结果显示RyRs在背根神经节(DRG)神经元表达。同样,钙成像在小DRG神经元说明,激活RyRs升高[Ca2+]iin小DRG neurons.ConclusionsThese数据表明,激活突触前RyRs起着至关重要的作用,在诱导LTP的脊髓疼痛通路,可能通过增强的递质释放。
BackgroundOur previous study demonstrated that nitric oxide (NO) contributes to long-term potentiation (LTP) of C-fiber-evoked field potentials by tetanic stimulation of the sciatic nerve in the spinal cordin vivo. Ryanodine receptor (RyR) is a downstream target for NO. The present study further explored the role of RyR in synaptic plasticity of the spinal pain pathway.ResultsBy means of field potential recordings in the adult male ratin vivo, we showed that RyR antagonist reduced LTP of C-fiber-evoked responses in the spinal dorsal horn by tetanic stimulation of the sciatic nerve. Using spinal cord slice preparations and field potential recordings from superficial dorsal horn, high frequency stimulation of Lissauer's tract (LT) stably induced LTP of field excitatory postsynaptic potentials (fEPSPs). Perfusion of RyR antagonists blocked the induction of LT stimulation-evoked spinal LTP, while Ins(1,4,5)P3 receptor (IP3R) antagonist had no significant effect on LTP induction. Moreover, activation of RyRs by caffeine without high frequency stimulation induced a long-term potentiation in the presence of bicuculline methiodide and strychnine. Further, in patch-clamp recordings from superficial dorsal horn neurons, activation of RyRs resulted in a large increase in the frequency of miniature EPSCs (mEPSCs). Immunohistochemical study showed that RyRs were expressed in the dorsal root ganglion (DRG) neurons. Likewise, calcium imaging in small DRG neurons illustrated that activation of RyRs elevated [Ca2+]iin small DRG neurons.ConclusionsThese data indicate that activation of presynaptic RyRs play a crucial role in the induction of LTP in the spinal pain pathway, probably through enhancement of transmitter release.
DOI: 10.1186/1744-8069-4-18
发表时间: 2008-05-28
期刊: MOLECULAR PAIN
影响因子: 3.3
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DOI: 10.1152/jn.00601.2002
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影响因子: 2.5
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