Effects of 3-benzidino-6-phenylpyridazine, as an acetylcholinesterase inhibitor, on outward potassium current in acutely isolated rat hippocampal pyramidal neurons

Toxicol Lett. 2008 Sep 26;181(2):104-11. doi: 10.1016/j.toxlet.2008.07.004. Epub 2008 Jul 15.

Abstract

As an acetylcholinesterase (AChE) inhibitor, the effects of 3-benzidino-6-phenylpyridazine (BPP) on outward potassium current including delayed rectifier potassium current (I(K(DR))) and transient outward potassium current (I(K(A))) in acutely isolated rat hippocampal pyramidal neurons were studied, using the whole cell patch-clamp technique. BPP reversibly inhibited electric eel AChE as an inhibitor, with IC(50) of 1.43 microM. BPP (0.10-100 microM) decreased I(K(DR)) and I(K(A)) in a concentration-dependent, voltage-independent and partial reversible manner, with IC(50) of 0.47 and 0.31 microM, respectively. 10 microM BPP did not affect steady-state activation of I(K(DR)) and I(K(A)). In addition, 10 microM BPP shifted the voltage dependence of steady-state inactivation of I(K(A)) towards negative potential. In conclusion, BPP potently inhibits I(K(DR)) and I(K(A)) in rat hippocampal pyramidal neurons, which may contribute to BPP's restoring the damaged central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholinesterase Inhibitors / pharmacology*
  • Delayed Rectifier Potassium Channels / drug effects
  • Delayed Rectifier Potassium Channels / physiology
  • Dose-Response Relationship, Drug
  • Electrophorus
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects*
  • Potassium Channels / physiology
  • Pyramidal Cells / drug effects*
  • Pyramidal Cells / metabolism
  • Pyridazines / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • 3-benzidino-6-phenylpyridazine
  • Cholinesterase Inhibitors
  • Delayed Rectifier Potassium Channels
  • Potassium Channels
  • Pyridazines