3-Benzidino-6(4-chlorophenyl) pyridazine blocks delayed rectifier and transient outward potassium current in acutely isolated rat hippocampal pyramidal neurons

Abstract

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.