Effects of donepezil on the delayed rectifier-like potassium current in pyramidal neurons of rat hippocampus and neocortex.
- Author:
Chong-bo ZHONG
1
;
Wei ZHANG
;
Xiao-liang WANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cholinesterase Inhibitors; pharmacology; Delayed Rectifier Potassium Channels; Hippocampus; cytology; In Vitro Techniques; Indans; pharmacology; Male; Neocortex; cytology; Neurons; drug effects; metabolism; Patch-Clamp Techniques; Piperidines; pharmacology; Potassium Channels; drug effects; physiology; Potassium Channels, Voltage-Gated; Pyramidal Cells; drug effects; metabolism; Rats; Rats, Wistar
- From: Acta Pharmaceutica Sinica 2002;37(6):415-418
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo investigat the effects of donepezil on delayed rectifier-like potassium currents (IK) in rat hippocampus and neocortex.
METHODSWhole cell configuration of the patch-clamp techniques were used to characterize IK in acutely isolated rat hippocampal and neocortical pyramidal neurons.
RESULTSThe 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).
CONCLUSIONAt 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.