Du Hui-Zhi, Zhang Chao-Feng, Li Miao-Yu, Yang Pin
Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, PR China.
Neurosci Lett. 2006 Jul 10;402(1-2):159-63. doi: 10.1016/j.neulet.2006.03.067. Epub 2006 May 2.
3-[(beta-morpholinoethyl)amino]-4-methyl-6-phenylpyridazine (minaprine) is an acetylcholinesterase (AChE) inhibitor. 3-Benzidino-6(4-chlorophenyl) pyridazine (BCP) and minaprine have a central pyridazine ring in common. In this study, we investigated the effects of BCP on delayed rectifier potassium current (IK(DR)) and transient outward potassium current (IK(A)) in acutely isolated rat hippocampal pyramidal neurons by using whole-cell patch-clamp technique. IK(DR) and IK(A) were inhibited by BCP (0.01-500 microM) in a concentration-dependent and voltage-dependent manner. The IC50 value for the blocking action of BCP on IK(DR) and IK(A) was calculated as 7.13+/-0.18 microM and 0.55+/-0.11 microM, respectively. At the concentration of 10 microM, BCP shifted the activation curve of IK(DR) to positive potential by 29.09 mV. Meanwhile, at the concentration of 10 microM, BCP also shifted the activation and inactivation curve of IK(A) to positive potential by 34.18 and 22.47 mV, respectively. In conclusion, BCP potently inhibits IK(DR) and IK(A) in rat hippocampal pyramidal neurons.
3-[(β-吗啉代乙基)氨基]-4-甲基-6-苯基哒嗪（米那普明）是一种乙酰胆碱酯酶（AChE）抑制剂。3-联苯胺基-6-(4-氯苯基)哒嗪（BCP）和米那普明具有共同的中心哒嗪环。在本研究中，我们采用全细胞膜片钳技术研究了BCP对急性分离的大鼠海马锥体细胞延迟整流钾电流（IK(DR)）和瞬时外向钾电流（IK(A)）的影响。BCP（0.01 - 500 μM）以浓度依赖性和电压依赖性方式抑制IK(DR)和IK(A)。BCP对IK(DR)和IK(A)阻断作用的IC50值分别计算为7.13±0.18 μM和0.55±0.11 μM。在10 μM浓度下，BCP使IK(DR)的激活曲线向正电位移动29.09 mV。同时，在10 μM浓度下，BCP也分别使IK(A)的激活和失活曲线向正电位移动34.18和22.4 mV。总之，BCP可有效抑制大鼠海马锥体细胞中的IK(DR)和IK(A)。
