Bis(7)-tacrine/tacrine对大鼠DRG神经元延时整流钾通道电流的调制作用

摘要

目的 研究乙酰胆碱酯酶抑制剂bis(7)-tacrine/tacrine[bis(7)-tetrahydroaminacrine]对大鼠DRG神经元的延时整流钾通道电流的调制作用.方法 在急性分离的DRG神经元标本上,采用全细胞膜片钳技术记录钾通道电流,研究bis(7)-tacrine/tacrine对DRG神经元延时整流钾通道电流的影响和作用.结果 bis(7)-tacrine对延迟整流钾通道电流IDR具有浓度依赖性的抑制作用,其半量效浓度为(IC50)(0.72±0.05)μmol*L-1,而tacrine抑制的半量效浓度(IC50)(58.3±3.7)μmol*L-1.结论 两种药物对DRG延时整流钾通道电流有浓度依赖性的抑制作用,bis(7)-tacrine的抑制强度高一个数量级,有利于抑制神经元的钾通道过于激活和兴奋,预防胞内钾离子过度丢失而引起的神经元凋亡,起到神经保护的作用.%Aim To investigate modulatory effect of bis ( 7 )-tacrine [ bis ( 7 )-tetrahydroaminacrine ], a novel dimeric AChE inhibitor, on rat DRG delayed rectified potassium channels. Methods Experiments were per -formed on neurons acutely isolated from rat dorsal root ganglion ( DRG ) potassium channels, and the delayed rectified currents ( IDR ) were recorded with whole-cell patch clamp technique. Results IDR were inhibited by bis( 7 )-tacrine, which were much more potent ( IC50 = 0. 72 ±0. 05 μmol · L-1 for IDR ) than those by tacrine ( IC50 =58. 3 ± 3. 7 μmol · L-1 for IDR ). bis( 7 )-tac-rine ( 1 μmol · L-1 ) shifts steady state activation curve and inactivation curve of IDR to the hyperpolar-izing direction. Conclusions The inhibitory effect of bis( 7 )-tacrine on IDR may be attributed to reduction of potential ranges of steady state activation and inactivation and delay of decay phase. Drugs may prevent loss of potassium ions and excitory toxicosis for neuron, and may be neuroprotective in A. D treatment.