Attenuated Glial K(+) Clearance Contributes to Long-Term Synaptic Potentiation Via Depolarizing GABA in Dorsal Horn Neurons of Rat Spinal Cord.
Attenuated Glial K(+) Clearance Contributes to Long-Term Synaptic Potentiation Via Depolarizing GABA in Dorsal Horn Neurons of Rat Spinal Cord.
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DOI：
10.5607/en.2014.23.1.53
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发表时间：
2014-03
影响因子：
2.4
通讯作者：
Whitsel BL
中科院分区：
文献类型：
--
作者：
Lee J;Favorov OV;Tommerdahl M;Lee CJ;Whitsel BL
据报道，长期增强的浅背角（DHs）兴奋性突触传递是中枢致敏、继发性痛觉过敏和持续疼痛的基础。我们测试了DHs中神经胶质细胞对K+和谷氨酸的清除受损是否有助于中枢神经系统疼痛回路和感觉运动异常的启动和维持。脊髓切片短暂暴露于氟柠檬酸盐（FC）中，可伴随对同侧背根重复性电刺激的DHs光学反应持续下降，同时DHs的突触后反应（如LTP）也同样持续增加。研究还表明，在APV存在的情况下，LTPFC不会发生，并且随着灌注液中的[K+]o从3.0 mM降低到0.0 mM， LTPFC逐渐变小。有趣的是，Bic溶液的应用降低了LTPFC。采用全细胞膜片记录来评估FC对DHs神经元对喷剂施加的GABA的反应的影响。观察结果表明，短暂暴露于FC确实伴随着GABA引起的DHs神经元跨膜离子电流平衡电位的长时间（bbb1hr）去极化移位。综合考虑，这些发现表明LTPFC涉及(1)DHs中[K+]o的升高，(2)NMDAR的激活，以及(3)GABA对DHs神经元的作用从抑制到兴奋的转化。有人提出，星形胶质细胞能量产生的短暂损伤可以触发背角机制的级联，这是痛觉过敏和持续疼痛的基础。
It has been reported that long-term enhancement of superficial dorsal horn (DHs) excitatory synaptic transmission underlies central sensitization, secondary hyperalgesia, and persistent pain. We tested whether impaired clearance of K+ and glutamate by glia in DHs may contribute to initiation and maintenance of the CNS pain circuit and sensorimotor abnormalities. Transient exposure of the spinal cord slice to fluorocitrate (FC) is shown to be accompanied by a protracted decrease of the DHs optical response to repetitive electrical stimulation of the ipsilateral dorsal root, and by a similarly protracted increase in the postsynaptic response of the DHs like LTP. It also is shown that LTPFC does not occur in the presence of APV, and becomes progressively smaller as [K+]o in the perfusion solution decreased from 3.0 mM to 0.0 mM. Interestingly LTPFC is reduced by bath application of Bic. Whole-cell patch recordings were carried out to evaluate the effects of FC on the response of DHs neurons to puffer-applied GABA. The observations reveal that transient exposure to FC is reliably accompanied by a prolonged (>1 hr) depolarizing shift of the equilibrium potential for the DHs neuron transmembrane ionic currents evoked by GABA. Considered collectively, the findings demonstrate that LTPFC involves (1) elevation of [K+]o in the DHs, (2) NMDAR activation, and (3) conversion of the effect of GABA on DHs neurons from inhibition to excitation. It is proposed that a transient impairment of astrocyte energy production can trigger the cascade of dorsal horn mechanisms that underlies hyperalgesia and persistent pain.