Enhancement by interleukin-1β of AMPA and NMDA receptor-mediated currents in adult rat spinal superficial dorsal horn neurons.

Enhancement by interleukin-1β of AMPA and NMDA receptor-mediated currents in adult rat spinal superficial dorsal horn neurons.
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DOI:
10.1186/1744-8069-9-16
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发表时间:
2013-03-28
期刊:
影响因子:
3.3
通讯作者:
Kumamoto E
Kumamoto E
中科院分区:
医学3区
文献类型:
--
作者:
Liu T;Jiang CY;Fujita T;Luo SW;Kumamoto E

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脊髓小胶质细胞释放的促炎细胞因子白细胞介素-1 β(IL-1β)在维持急性和慢性疼痛状态中起重要作用。然而,这种作用的细胞基础仍然知之甚少。采用全细胞膜片钳技术,研究了IL-1β对成年大鼠脊髓片胶状质(SG)神经元AMPA和NMDA受体介导电流的作用,SG神经元是调节外周伤害性信息传递的关键部位。在SG神经元中,IL-1β以彼此不同的方式增加AMPA和NMDA诱导的电流的峰值幅度。IL-1β的这些易化作用可被IL-1受体(IL-1 R)拮抗剂(IL-1 ra)所消除,而IL-1 ra本身对AMPA和NMDA诱导的电流没有可检测到的作用。在IL-1β洗脱后30 min,IL-1β易化的AMPA诱导的电流恢复至对照水平,在Na+通道阻断剂河豚毒素或名义上无Ca 2+的Krebs溶液中,AMPA诱导的电流大部分被抑制。米诺环素,一种小胶质细胞抑制剂,阻断了IL-1β对AMPA诱导的电流的易化作用,而不是NMDA诱导的电流,其中米诺环素本身抑制NMDA-,但对AMPA诱导的电流没有任何影响。IL-1β通过IL-1 R激活增强SG神经元中的AMPA和NMDA反应;前者而非后者的作用是可逆的,并且是由于神经元活性以依赖于细胞外Ca 2+和米诺环素的方式增加。提示AMPA和NMDA受体受IL-1β不同方式的正性调节;前者是由神经元活动增加释放的神经递质介导的,而后者不是。由于IL-1β参与外周神经或组织损伤诱导的伤害性行为,本研究结果还揭示了脊髓背角神经元和胶质细胞之间的重要细胞联系。
Proinflammatory cytokine interleukin-1β (IL-1β) released from spinal microglia plays an important role in the maintenance of acute and chronic pain states. However, the cellular basis of this action remains poorly understood. Using whole-cell patch-clamp recordings, we examined the action of IL-1β on AMPA- and NMDA-receptor-mediated currents recorded from substantia gelatinosa (SG) neurons of adult rat spinal cord slices which are key sites for regulating nociceptive transmission from the periphery. AMPA- and NMDA-induced currents were increased in peak amplitude by IL-1β in a manner different from each other in SG neurons. These facilitatory actions of IL-1β were abolished by IL-1 receptor (IL-1R) antagonist (IL-1ra), which by itself had no detectable effects on AMPA- and NMDA-induced currents. The AMPA- but not NMDA-induced current facilitated by IL-1β was recovered to control level 30 min after IL-1β washout and largely depressed in Na+-channel blocker tetrodotoxin-containing or nominally Ca2+-free Krebs solution. Minocycline, a microglia inhibitor, blocked the facilitatory effect of IL-1β on AMPA- but not NMDA-induced currents, where minocycline itself depressed NMDA- but had not any effects on AMPA-induced currents. IL-1β enhances AMPA and NMDA responses in SG neurons through IL-1R activation; the former but not latter action is reversible and due to an increase in neuronal activity in a manner dependent on extracellular Ca2+ and minocycline. It is suggested that AMPA and NMDA receptors are positively modulated by IL-1β in a manner different from each other; the former but not latter is mediated by a neurotransmitter released as a result of an increase in neuronal activity. Since IL-1β contributes to nociceptive behavior induced by peripheral nerve or tissue injury, the present findings also reveal an important cellular link between neuronal and glial cells in the spinal dorsal horn.
DOI: 10.1523/jneurosci.3295-09.2010
发表时间: 2010-01-13
期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子: --
作者:
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发表时间: 2012-01-01
期刊: PHARMACOLOGY
影响因子: 3.1
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Jin, Ling-Jing;Schlesinger, Friedrich;Nie, Zhi-Yu
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DOI: 10.1523/jneurosci.3795-08.2008
发表时间: 2008-12-24
期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子: --
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发表时间: 2002-04-01
影响因子: 5.5
作者:
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发表时间: 1997-06-06
期刊: BRAIN RESEARCH
影响因子: 2.9
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通讯作者: Rickman, AJ