Zhang X-L, Lee K-Y, Priest B T, Belfer I, Gold M S
Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Lilly Research Laboratories, Indianapolis, IN 46285, USA.
Neuroscience. 2015 Dec 3;310:401-9. doi: 10.1016/j.neuroscience.2015.09.048. Epub 2015 Sep 28.
The purpose of the present study was to characterize the properties of A-type GABA receptor (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, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol (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.
本研究的目的是表征人类感觉神经元中 A 型γ-氨基丁酸受体（GABAA 受体）电流的特性。神经元取自成年器官捐赠者。在分离的神经元中记录 GABAA 电流。在来自 15 名捐赠者的 129 个研究神经元中均存在大的失活低亲和力电流和较小的持续性高亲和力电流。人类 GABAA 电流的动力学比大鼠感觉神经元中的动力学慢。GABA 电流被荷包牡丹碱（10 μM）完全阻断，持续性电流被δ亚基偏好激动剂 4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇（THIP）激活。GABA 电流平衡电位比大鼠神经元中的超极化约 20 mV。低亲和力和高亲和力电流均被炎症介质增加，但通过不同的第二信使途径。这些结果突出了其天然环境中存在的离子通道特性中潜在的重要物种差异，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工具。
