Donepezil对大鼠海马及新皮层锥体神经元延迟整流样钾电流的影响

目的探讨donepezil对大鼠海马和新皮层锥体神经元具有延迟整流样特性钾电流(I_K)的影响。方法 用膜片钳全细胞记录法。结果Donepezil在微摩尔水平即可抑制I_K,并呈剂量依赖性和电压依赖性,且可使I_K的稳态激活曲线向超级化的方向移动。结论低浓度donepezil即可抑制大鼠海马和新皮层锥体神经元电压激活的I_K,此作用可能与其抑制胆碱酯酶活性协同,参与药物的治疗效应。

EFFECTS OF DONEPEZIL ON THE DELAYED RECTIFIER-LIKE POTASSIUM CURRENT IN PYRAMIDAL NEURONS OF RAT HIPPOCAMPUS AND NEOCORTEX

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.