Donepezil in low micromolar concentrations modulates voltage-gated potassium currents in pyramidal neurons of rat hippocampus |
| |
| Authors: | Elena I Solntseva Julia V Bukanova Vladimir G Skrebitsky |
| |
| Institution: | 1. ICBMS, UMR CNRS 5246, University of Lyon 1, Bâtiment Raulin, 43 Bd du 11 novembre 1918, 69622 Villeurbanne Cedex, France;2. Physiopathology of Inflammatory Bone Diseases, EA4490, ULCO. Quai Masset, Bassin Napoléon BP120, 62327 Boulogne/Mer, France;3. Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14, Switzerland;1. Centre for Cognition and Decision Making, National Research University Higher School of Economics, Russian Federation;2. Department of Neurosurgery, Unispital Zurich, University of Zurich, Switzerland;3. Laboratory of Neuroscience and Molecular Pharmacology, Institute of Translational Biomedicine, Saint Petersburg State University, Russian Federation;4. Research Center of Neurology, Moscow, Russian Federation;5. Neurophysics Group, Department of Neurology, Charité – University Medicine Berlin, Germany;1. Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, 119991 Moscow, Russia;2. Research Center of Neurology, 125367 Moscow, Russia;1. Department of Cell Physiology, Ruhr University Bochum, 44801 Bochum, Germany;2. National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan;3. Philip Morris International R&D, Philip Morris Products SA, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland |
| |
| Abstract: | Donepezil is a cholinesterase inhibitor widely used for the treatment of Alzheimer’s disease. Voltage-gated K+-channels are discussed as possible targets for the drug, but the results obtained by different authors are contradictory. In the present study performed on pyramidal cells isolated from rat’s hippocampus, we investigated the effect of donepezil on delayed rectifier K+-current (IK(DR)) and transient outward K+-current (IK(A)) using patch-clamp technique. The inhibitory effect of donepezil on IK(DR) was found in all the cells tested, but its strength varied in different cells. Two groups of neurons were differing in their sensitivity to donepezil: more sensitive (IC50 = 8.9 μM) and less sensitive (IC50 = 114.9 μM). The effect of the drug on IK(DR) was rapid, reversible and voltage-dependent, increasing with depolarization. Donepezil modulated IK(A) in two different ways: in some cells it suppressed the current with the IC50 value of 23.4 μM, while in other cells it augmented the current with a bell-shaped dose–response curve. Maximal (about twofold) enhancement of IK(A) amplitude was caused by 10 μM donepezil. Augmentation of IK(A) increased with membrane depolarization. Our results show for the first time that voltage-dependent potassium channels in mammals’ neurons are effectively modulated by low micromolar concentrations of donepezil. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
