[Effects of donepezil on the delayed rectifier-like potassium current in pyramidal neurons of rat hippocampus and neocortex]
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Published on: September 5, 2015
Chong-bo Zhong1, Wei Zhang, Xiao-liang Wang
1Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Aim:
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).
Conclusion:
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.
