Galantamine blocks cloned Kv2.1, but not Kv1.5 potassium channels.
Galantamine is a cholinesterase inhibitor (AChEI) currently used in treatment of Alzheimer's disease (AD). In the present study, the effects of galantamine on currents of cloned Kv2.1 and Kv1.5 potassium channels were investigated by using patch-clamp whole cell recording techniques. Kv2.1 and Kv1.5 were stably expressed in HEK293 cells. Galantamine blocked Kv2.1 current in a concentration-dependent manner. When depolarizing from -50 to +40 mV, the IC50 of galantamine for inhibition of Kv2.1 was 5.6 microM. Galantamine 10 microM shifted the activation curve of Kv2.1 to negative potential by 4.0 mV. At the same concentration, galantamine shifted the inactivation curve to negative potential by 25.2 mV. While Kv1.5 was not sensitive to galantamine, Kv1.5 current was not changed by galantamine at concentration of 10 microM. Our data suggest that galantamine potently blocks Kv2.1, but not Kv1.5 channels.
Zhang
Hai-Xia
HX
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, PR China.
Zhang
Wei
W
Jin
Hong-Wei
HW
Wang
Xiao-Liang
XL
D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003001:Cloning, Molecular; D005702:Galantamine / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000166:cytology; D051666:Kv1.5 Potassium Channel; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000378:metabolism*; D051669:Shab Potassium Channels
D002800:Cholinesterase Inhibitors; C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D024642:Potassium Channels, Voltage-Gated; D051669:Shab Potassium Channels; D005702:Galantamine; D011188:Potassium