Modulation of excitatory synaptic transmission in the spinal substantia gelatinosa of mice deficient in the kainate receptor GluR5 and/or GluR6 subunit

Modulation of excitatory synaptic transmission in the spinal substantia gelatinosa of mice deficient in the kainate receptor GluR5 and/or GluR6 subunit
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红藻氨酸受体 GluR5 和/或 GluR6 亚基缺陷小鼠脊髓胶质中兴奋性突触传递的调节

DOI:
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发表时间:
2004
期刊:
Journal of Physiology
影响因子:
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通讯作者:
M. Randić
M. Randić
中科院分区:
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文献类型:
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作者:
Dong‐ho Youn and;M. Randić

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功能性kainate (KA)受体(KARs)在脊髓明胶质(SG)区域表达,其激活具有调节与SG神经元的初级传入突触的兴奋性突触传递的能力。在本研究中,我们使用缺乏KAR GluR5和/或GluR6亚基的基因靶向小鼠来确定参与KA诱导的兴奋性传递调节的受体亚基的身份。我们的研究结果表明,含有GluR5或GluR6亚基的KARs可以抑制或促进急性制备的成年小鼠脊髓切片SG中的谷氨酸能兴奋传递。在GABAA和甘氨酸受体介导的突触抑制缺失的情况下,盐酸盐的双相作用表现为低浓度(30 nm)的诱导作用和高浓度(3 μm)的抑制作用。此外,定位于突触前和突触后的GluR6‐KARs在抑制a δ和C纤维单突触通路的传输中起关键作用,而突触前GluR5‐KARs在抑制C纤维激活通路中起有限作用。这些结果支持了KARs参与脊髓SG区兴奋性突触传递的双向调节的假设,并且这些作用可能对伤害感觉和疼痛的临床治疗至关重要。
Functional kainate (KA) receptors (KARs) are expressed in the spinal cord substantia gelatinosa (SG) region, and their activation has a capacity to modulate excitatory synaptic transmission at primary afferent synapses with SG neurones. In the present study, we have used gene‐targeted mice lacking KAR GluR5 and/or GluR6 subunits to determine the identity of the receptor subunits involved in the KA‐induced modulation of excitatory transmission. Our findings reveal that KARs comprising GluR5 or GluR6 subunits can either suppress or facilitate glutamatergic excitatory transmission in the SG of acutely prepared adult mouse spinal cord slices. In the absence of synaptic inhibition mediated by GABAA and glycine receptors, a biphasic effect of kainate is characteristic with facilitation apparent at a low concentration (30 nm) and depression at a higher concentration (3 μm). In addition, GluR6‐KARs, localizing pre‐ and postsynaptically, are critically involved in inhibiting transmission at both Aδ and C fibre monosynaptic pathways, whereas presynaptic GluR5‐KARs play a limited role in inhibiting the C fibre‐activated pathway. The results obtained support the hypothesis that KARs are involved in bi‐directional regulation of excitatory synaptic transmission in the spinal cord SG region, and that these actions may be of critical importance for nociception and the clinical treatment of pain.
DOI: 10.1016/s0014-2999(02)02333-6
发表时间: 2002-10-11
影响因子: 5
作者:
Guo, W;Zou, SP;Ren, K
通讯作者: Ren, K