可溶性Aβ25-35对大鼠海马CA3区神经元延迟整流钾电流的抑制作用  

Inhibitory Effect of Unaggregated Amyloid β Protein (25-35) on Delayed Rectifier Potassium Current in Rat Hippocampal CA3 Pyramidal Neurons

作　　者：李琳[1] 刘振宅[2] 贺秉军[3] 戚豫[1] 

机构地区：[1]北京大学第一医院中心实验室,北京100034 [2]天津医科大学生物医学工程系,天津300070 [3]南开大学生命科学学院,天津300071

出　　处：《中国医学科学院学报》2008年第3期301-304,共4页Acta Academiae Medicinae Sinicae

摘　　要：目的研究可溶性β-淀粉样蛋白(Aβ25-35)对大鼠海马CA3区锥体神经元延迟整流钾电流(IK)的影响。方法采用酶消化法急性分离新生大鼠海马CA3区神经元,全细胞膜片钳技术观察加入可溶性Aβ25-35后IK的变化。结果可溶性Aβ25-35对IK的作用具有时间依赖性,IK随Aβ25-35作用时间的延长而减小,加药5～7min后作用趋于稳定。可溶性Aβ25-35对IK有明显抑制作用,加入5μmol/LAβ25-35前后IK峰值分别为(6.987±1.152)和(2.540±0.349)nA(n=8,P<0.01);该抑制作用没有明显的浓度依赖性,1、2.5和5μmol/L3个浓度的Aβ25-35使IK峰值减小率都在60%左右。5μmol/LAβ25-35可显著影响IK激活过程,作用前后的半数激活电压分别为(4.114±0.730)和(-5.463±0.950)mV(n=15,P<0.05),但不改变激活曲线的斜率因子。结论可溶性Aβ25-35对海马CA3区神经元IK的抑制作用可能是其产生神经毒性的作用机制之一。Objective To investigate the effect of unaggregated Aβ25-35 on delayed rectifier potassium current （IK ） in neonatal rat hippocampal CA3 pyramidal neurons. Methods The rat hippocampal neurons were enzymatically isolated from 10-11-day-old Wistar rat. The IK was recorded using whole-cell patch clamp technique. Results The inhibitory effect of unaggregated Aβ25-35 on IK was time-dependent, because Ik significantly decreased from （ 6. 987 ± 1. 152 ） nA to （ 2. 540 ± 0. 349 ） nA after adding unaggregated Aβ25.35 and reached a stabilized level after 5-7 min （n = 8, P 〈0.01 ）. However, the inhibitory effect was not concentration-dependent, because the decrease of the IK amplitude in different concentration groups were all around 60%. Unaggregated Aβ25-35 also remarkably affected the and （ - 5. 463 ± 0. 950 ） mV before and after its of activation curve was not significantly changed half-activation potential, which was （4.114 ± 0. 730 ） mV application （ n = 15, P 〈 0.05） ; however, the slope factor Conclusion The inhibitory effect of unaggregated Aβ25-35 on Ik may be a possible mechanism involved in the pathogenesis of Alzheimer＇s disease.

关 键 词：阿尔茨海默病 可溶性β-淀粉样蛋白 海马CA3区锥体神经元 延迟整流钾电流 全细胞膜片钳 

分 类 号：R338[医药卫生—人体生理学] Q426[医药卫生—基础医学]