Kv2.1钾通道在神经元缺氧损伤中的潜在药理学作用  

Potential Pharmacologic Role of Kv2.1 Potassium Channel in Ischemic Neuron Injury

作　　者：袁辉[1] 王伟平[1] 马士平[1] 刘斌[1] 徐少峰[1] 冯楠[1] 李江[1] 王玲[1] 王晓良[1] 

机构地区：[1]中国医学科学院-北京协和医学院药物研究所,北京100050

出　　处：《中国药学杂志》2009年第6期436-439,共4页Chinese Pharmaceutical Journal

摘　　要：目的观察钾通道阻断剂四乙铵(TEA)对缺氧缺血损伤整体、离体模型的保护作用,阐明Kv2.1电压依赖性钾通道在缺氧缺血细胞损伤中发挥的作用。方法应用大鼠暂时性大脑中动脉阻塞(tMCAO)脑缺血模型验证TEA对脑缺血损伤的保护作用。采用膜片钳技术观察氧糖剥夺(OGD)对稳定转染Kv2.1钾通道的人胚胎肾293(HEK293)细胞膜电位以及TEA对OGDKv2.1-HEK293细胞钾电流的影响。MTT法观察OGD对Kv2.1-HEK293的损伤及TEA的保护作用。结果TEA(5μg·kg-1)侧脑室注射可以显著减小tMCAO大鼠的脑梗死体积;应用转基因细胞的研究证实Kv2.1-HEK293对OGD损伤的敏感性明显提高;OGD可以降低Kv2.1-HEK293细胞膜电位;TEA(10mmol·L-1)能显著抑制OGDKv2.1-HEK293钾电流,同时使其所受的细胞损伤降低。结论钾通道阻断剂TEA对整体和离体缺氧缺血损伤模型均发挥细胞保护作用,这种保护作用与对Kv2.1的阻断密切相关;提示Kv2.1可能是抗脑缺血药物开发的潜在靶点。OBJECTIVE To measure the neuroprotective effect of IK channel blocker tetraethylammonium （TEA） against hypoxia/ischemia-induced cell death in vitro or in vivo and to investigate the role of outward delayed rectifier （IK） channel Kv2.1 in hypoxia/ischemia-induced cell damage. METHODS Whole cell potassium currents and membrane potential were recorded with the use of patch-clamp recordings in cultured Kv2.1-HEK293 cells and blank cells. Hypoxia and ischemia-induced cell death and effects of TEA were measured by MTT method in vitro and tMCAO in vivo. RESULTS Membrane potential of Kv2.1-HEK293 cell moved toward depolarization direction after being treated by oxygen and glucose deprivation （OGD）. TEA blocked OGD Kv2. 1-HEK293 IK currents and showed protective effects against hypoxia/ischemia-induced cell death in vitro（10 mmol.L^-1） and in vivo（5 μg.kg^-1）. CONCLUSION Protective effects of TEA against hypoxia/ischemia-induced cell death in vitro and in vivo are closely related to outward delayed rectifier （/K） channel Kv2.1. It suggests that the block of excessive K＋ efflux through Kv2.1 channel may constitute a therapeutic approach for the treatment of stroke.

关 键 词：Kv2.1 脑缺血 氧糖剥夺 四乙铵 

分 类 号：R969[医药卫生—药理学]