Inflammatory mediator-induced modulation of GABAA currents in human sensory neurons.
Inflammatory mediator-induced modulation of GABAA currents in human sensory neurons.
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DOI：
10.1016/j.neuroscience.2015.09.048
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发表时间：
2015-12-03
期刊：
影响因子：
3.3
通讯作者：
Gold MS
中科院分区：
文献类型：
--
作者：
Zhang XL;Lee KY;Priest BT;Belfer I;Gold MS
本研究的目的是表征人类感觉神经元中 GABAA 受体电流的特性。神经元是从成人器官捐献者那里获得的。在孤立的神经元中记录 GABAA 电流。在来自 15 名供体的所有 129 个神经元中，都存在较大的失活低亲和力电流和较小的持续高亲和力电流。人类 GABAA 电流的动力学比大鼠感觉神经元的动力学慢。 GABA 电流被荷包牡丹碱 (10 µM) 完全阻断，持续电流被 δ 亚基偏好激动剂 THIP 激活。 GABA 电流平衡电位比大鼠神经元中的超极化程度高约 20 mV。低亲和力电流和高亲和力电流均通过炎症介质增加，但通过不同的第二信使途径。这些结果强调了天然环境中存在的离子通道特性的潜在重要物种差异，并表明使用人类感觉神经元可能是在用于人类之前测试化合物的有价值的工具。
The purpose of the present study was to characterize the properties of GABAA receptor currents in human sensory neurons. Neurons were obtained from adult organ donors. GABAA currents were recorded in isolated neurons. Both large inactivating low affinity currents and smaller persistent high affinity currents were present in all of the 129 neurons studied from 15 donors. The kinetics of human GABAA currents were slower than those in rat sensory neurons. GABA currents were completely blocked by bicuculline (10 µM), and persistent currents were activated by the δ-subunit preferring agonist, THIP. The GABA current equilibrium potential was ~20 mV more hyperpolarized than in rat neurons. Both low and high affinity currents were increased by inflammatory mediators but via different second messenger pathways. These results highlight potentially important species differences in the properties of ion channels present in their native environment and suggest the use of human sensory neurons may be a valuable tool to test compounds prior to use in humans.