Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord
Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord
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作者：
Li, P;Wilding, TJ;Zhuo, M
谷氨酸是中枢神经系统中的主要兴奋性神经递质，激活直接门控离子通道的三种不同受体，即AMPA（α-氨基-3-羟基-5-甲基异氧唑丙酸）、NMDA（N-甲基-D-天冬氨酸）和红藻氨酸（谷氨酸的结构类似物）的受体。AMPA和NMDA受体对突触传递和可塑性的贡献已得到充分证实（1）。最近关于红藻氨酸受体生理功能的研究集中在海马体（2），其中苔藓纤维途径的重复激活产生缓慢的红藻氨酸受体介导的兴奋性突触后电流（EPSC）（3-5）。在这里，我们表明，高强度的单次电击刺激（持续时间200微秒）的初级传入感觉纤维产生一个快速的，红藻氨酸受体介导的EPSC在脊髓的浅表背角。低阈值传入纤维的激活仅产生典型的AMPA受体介导的EPSC，表明红藻氨酸受体可能仅限于由高阈值伤害性（疼痛感测）和热感受性初级传入纤维形成的突触。与这种可能性相一致的是，红藻氨酸受体介导的EPSC被镇痛μ阿片受体激动剂Damgo阻断，并且红藻氨酸和AMPA受体两者的脊髓阻断产生抗伤害感受。因此，脊髓红藻氨酸受体有助于将体感输入从外周传递到大脑。
Glutamate, the major excitatory neurotransmitter in the central nervous system, activates three different receptors that directly gate ion channels, namely receptors for AMPA (alpha-amino-3-hydroxy-5-methyl isoxozole propionic acid), NMDA (N-methyl-D-aspartate), and kainate, a structural analogue of glutamate. The contribution of AMPA and NMDA receptors to synaptic transmission and plasticity is well established(1). Recent work on the physiological function of kainate receptors has focused on the hippocampus(2), where repetitive activation of the mossy-fibre pathway generates a slow, kainate-receptor-mediated excitatory postsynaptic current (EPSC)(3-5). Here we show that high-intensity single-shock stimulation (of duration 200 microseconds) of primary afferent sensory fibres produces a fast, kainate-receptor-mediated EPSC in the superficial dorsal horn of the spinal cord. Activation of low-threshold afferent fibres generates typical AMPA-receptor-mediated EPSCs only, indicating that kainate receptors may be restricted to synapses formed by high-threshold nociceptive (pain-sensing) and thermoreceptive primary afferent fibres. Consistent with this possibility, kainate-receptor-mediated EPSCs are blocked by the analgesic mu-opiate-receptor agonist Damgo and spinal blockade of both kainate and AMPA receptors produces antinociception, Thus, spinal kainate receptors contribute to transmission of somatosensory inputs from the periphery to the brain.