(1R,2R)-SIPI5358和SIPI5358对未分化PC12细胞延迟整流钾电流的抑制作用  

Inhibition of(1R,2R)-SIPI5358 and SIPI5358 on Delayed Rectifier Potassium Current in Undifferentiated PC12 Cells

作　　者：周慧[1] 汪溪洁[1] 翁志洁[2] 马璟[1] 李建其[2] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院,国家上海新药安全评价研究中心,上海201203 [2]中国医药工业研究总院上海医药工业研究院,上海200040

出　　处：《中国医药工业杂志》2012年第6期443-447,共5页Chinese Journal of Pharmaceuticals

基　　金：国家“十二五”重大新药创制科技重大专项(2012ZX09102-101-008)

摘　　要：利用全细胞膜片钳技术研究新化合物(1R,2R)-SIPI5358和SIPI5358对未分化PC12细胞延迟整流钾电流(IK)的影响。结果表明,(1R,2R)-SIPI5358和SIPI5358可抑制未分化PC12细胞的IK,且抑制作用具有浓度和电压依赖性,IC50分别为(0.64±0.17)和(12.05±3.31)mol/L。1 mol/L的(1R,2R)-SIPI5358可使未分化PC12细胞的IK稳态激活曲线和失活曲线向超极化方向移动4和20 mV。20 mol/L的SIPI5358可使未分化PC12细胞的IK稳态激活曲线向去极化方向移动7mV;使失活曲线向超极化方向移动21 mV。(1R,2R)-SIPI5358和SIPI5358对IK的影响可能与其神经毒性有关。The effects of（1R,2R）-SIPI5358 and SIPI5358 on the delayed rectifier potassium current（IK） in undifferentiated PC12 cells were recorded with whole-cell patch clamp technique.The results showed that the two compounds had a concentration-and voltage-dependent inhibition on IK.The IC50 values of（1R,2R）-SIPI5358 and SIPI5358 were（0.64±0.17） and（12.05±3.31）μmol/L,respectively.The（1R,2R）-SIPI5358 at the concentration of 1 μmol/L shifted the IK steady-state activation and inactivation curves in the hyperpolarizing direction by 4 and 20 mV.The SIPI5358 at the concentration of 20 μmol/L shifted the IK steady-state activation curve in the depolarizing direction by 7 mV and shifted the inactivation curve in the hyperpolarizing direction by 21 mV.The effects of（1R,2R）-SIPI5358 and SIPI5358 on IK might be related to their neurotoxicity.

关 键 词：(1R 2R)-SIPI5358 SIPI5358 未分化PC12细胞 延迟整流钾电流 全细胞膜片钳 

分 类 号：R965[医药卫生—药理学]