二氧化硫衍生物对大鼠海马神经元外向钾电流特性的影响(英文)

Influence of Sulfur dioxide derivatives on outward potassium current in rat hipp ocampal neurons

背景:二氧化硫(SO2)及其衍生物是细胞染色体断裂剂和基因毒性因子,还可引起机体组织的氧化损伤和酶活性的改变。但是,从膜损伤的角度来研究SO2及其代谢衍生物的毒作用,特别是神经毒效应,尚不十分清楚。目的:研究大鼠海马神经元去极化激活的外向钾电流的特征,并在此基础上初步探讨SO2衍生物对此外向电流的影响。设计:完全随机设计,自身对照实验对照。地点和材料:本研究的地点为山西大学环境医学与毒理学研究所。材料为Wistar大鼠,约40只,鼠龄7d,体重8～10g,雌雄不限。中国辐射防护研究院动物房提供。干预:利用全细胞膜片钳技术。主要观察指标:短时去极化至-60mV以上电位引发的外向电流;SO2衍生物作用前后此外向电流幅度的变化。结果:短时去极化至-60mV以上电位可引发快速上升的外向电流,之后缓慢衰减至一平台。当保持电位改变时,该峰电流与平台电流的幅度均会发生变化,但变化幅度不同,提示此外向电流包括两种成分。试验中测得峰电流与平台电流的翻转电位分别为(-76.1±5.97)mV和(-83.6±4.13)mV,与用Nerst方程计算出的本试验细胞外液与电极内液的钾离子平衡电位Ek=-88mV接近,说明该外向电流是钾电流。SO2衍生物可剂量依赖地增大此两种成分的外向钾电流,使二者增大50%的剂量分别为26.19μmol/L和14.

BACKGROUND:Sulfur dioxide(SO2) and its derivatives are recognized as the facto rs responsible for cellular chromosome cleavage and genotoxicity and capable of inducing oxidative injury and changes in enzyme activity.The toxicity of SO2 and its derivatives, from the perspective of cell membrane injuries and neurotoxic effects in particular, remains currently unclear. OBJECTIVE:To study the characteristics of depolarization-activated potassium current in rat hippocampal neurons,and observe the changes in the current in res ponse to cell treatment with SO2 and its derivatives. DESIGN: Completely randomized self-controlled study. SETTING and PARTICIPANTS:This study was conducted in the Institute of Environm ental Medicine of Shanxi University.Forty 7-day-old Wistar rats weighing 8 to 10 g of either sex were provided by the Experimental Animal Center of China Inst itute for Radiation Protection. INTERVENTION:Whole-cell patch-clamp technique was used. MAIN OUTCOME MEASURE:Outward current elicited by transient depolarization to o ver -60 mV was recorded and the changes in the amplitude of the current were ob served after stimulation with SO2 derivatives. RESULTS:Transient depolarization to over -60 mV could induce rapidly increase d outward current,which slowly attenuated to a plateau level.Changes in the hold ing potentials elicited peak and plateau current changes,but their amplitude cha nges varied,indicating that the outward current consisted two components. The re versal potentials of the peak and plateau currents were-76.1±5.97 and -83.6± 4.13 mV, respectively, similar to potassium equilibrium potential(Ek=-88 mV) be tween extracelluar and intra-electrode fluid calculated by Nerst equation,sugge sting that the outward current was potassium current.SO2 derivatives could ampli fy the two components of the outward K+current dose-dependently,and their dose s for 50%increment of the two components were 26.19 and 14.50 μmol/L respectiv ely. CONCLUSION:Sulfur dioxide derivatives can amplify voltage-dependent outward K +current in rat hippocampal neurons to cause central nervous system injury as a result of excessive intracellular potassium outflow through K+channels and int racellular K+loss.