Persistent inflammation increases GABA-induced depolarization of rat cutaneous dorsal root ganglion neurons in vitro.
Persistent inflammation increases GABA-induced depolarization of rat cutaneous dorsal root ganglion neurons in vitro.
复制标题
持续的炎症会增加GABA诱导的大鼠皮肤背根神经神经元的去极化。
DOI：
10.1016/j.neuroscience.2012.06.025
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发表时间：
2012-09-18
期刊：
影响因子：
3.3
通讯作者：
Gold, M. S.
中科院分区：
文献类型：
--
作者：
Zhu, Y.;Lu, S. G.;Gold, M. S.
持续性炎症与脊髓GABAA信号传导从抑制到兴奋的转变相关，使得GABAA受体活化有助于炎性痛觉过敏。我们检验了这样一个假设，即初级传入是持续炎症诱导的GABAA信号转移的部位，这是由于GABAA电流平衡电位（EGABA）的Na+-K+-Cl−-共转运蛋白（NKCC 1）依赖性去极化所致。采用Ca 2+成像、蛋白质印迹和短杆菌肽穿孔斑片记录法研究了幼稚和炎症（皮下注射完全弗氏佐剂后3天）成年雄性大鼠的急性分离的逆行标记皮肤背根神经节（DRG）神经元。GABA诱发的Ca 2+瞬态的小到中等直径的辣椒素敏感的皮肤神经元的亚群。炎症与GABA诱导的去极化幅度的显著增加以及GABA诱发Ca 2+瞬变的神经元的百分比相关。在整个神经节水平上，NKCC 1蛋白或磷蛋白没有检测到变化。此外，兴奋性反应的增加在HEPES和HCO 3 −缓冲溶液中相当，但仅与HCO 3 −基溶液中EGABA的去极化相关。相反，在这两种记录条件下，兴奋性反应与GABAA电流密度的增加，低阈值K+电流密度的减少，和静息膜电位去极化。我们的研究结果表明，增加K+电导的传入神经支配的持续性炎症部位可能有更大的疗效比试图驱动超极化转变EGABA的抑制炎性痛觉过敏。
Persistent inflammation is associated with a shift in spinal GABAA signaling from inhibition to excitation such that GABAA-receptor activation contributes to inflammatory hyperalgesia. We tested the hypothesis that the primary afferent is the site of the persistent inflammation-induced shift in GABAA signaling which is due to a Na+-K+-Cl−-co-transporter (NKCC1)-dependent depolarization of the GABAA current equilibrium potential (EGABA). Acutely dissociated retrogradely labeled cutaneous dorsal root ganglion (DRG) neurons from naïve and inflamed (3 days after a subcutaneous injection of complete Freund’s adjuvant) adult male rats were studied with Ca2+ imaging, western blot and gramicidin perforated patch recording. GABA evoked a Ca2+ transient in a subpopulation of small- to medium-diameter capsaicin-sensitive cutaneous neurons. Inflammation was associated with a significant increase in the magnitude of GABA-induced depolarization as well as the percentage of neurons in which GABA evoked a Ca2+ transient. There was no detectable change in NKCC1 protein or phosphoprotein at the whole ganglia level. Furthermore, the increase in excitatory response was comparable in both HEPES- and HCO3−-buffered solutions, but was only associated with a depolarization of EGABA in HCO3−-based solution. In contrast, under both recording conditions, the excitatory response was associated with an increase in GABAA current density, a decrease in low threshold K+ current density, and resting membrane potential depolarization. Our results suggest that increasing K+ conductance in afferents innervating a site of persistent inflammation may have greater efficacy in the inhibition of inflammatory hyperalgesia than attempting to drive a hyperpolarizing shift in EGABA.
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