[Effects of donepezil on the delayed rectifier-like potassium current in pyramidal neurons of rat hippocampus and neocortex].
OBJECTIVE
To investigat the effects of donepezil on delayed rectifier-like potassium currents (IK) in rat hippocampus and neocortex.


METHODS
Whole cell configuration of the patch-clamp techniques were used to characterize IK in acutely isolated rat hippocampal and neocortical pyramidal neurons.


RESULTS
The slowly inactivating outward currents (IK) were recorded in all cells under investigation. Donepezil in micromolar concentrations were shown to supress the IK of all cells in a dose-dependent and voltage-dependent manner. The steady-state activation curves of IK were characterized by half-activation potentials of -15.5 mV in hippocampal and -4.1 mV in neocortical pyramidal neurons and were changed to -26.2 mV and -18.6 mV, respectively, after perfusion with donepezil (10 mumol.L-1).


CONCLUSIONS
At concentrations as low as 1 mumol.L-1, donepezil was found to block the IK in a voltage-dependent manner in hippocampus and neocortex. This effect may be synergistic with the anticholinesterase activity of donepezil to increase its therapeutic effectiveness.
Zhong
Chong-bo
CB
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Zhang
Wei
W
Wang
Xiao-liang
XL
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D051668:Delayed Rectifier Potassium Channels; D000077265:Donepezil; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology*; D008297:Male; D019579:Neocortex / Q000166:cytology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002800:Cholinesterase Inhibitors; D051668:Delayed Rectifier Potassium Channels; D007189:Indans; D010880:Piperidines; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D000077265:Donepezil