Galantamine blocks delayed rectifier, but not transient outward potassium current in rat dissociated hippocampal pyramidal neurons.
Galantamine is an acetylcholinesterase inhibitor in Alzheimer's disease therapy. In the present study, we investigated the effects of galantamine on delayed rectifier potassium current (I(K(DR))) and transient outward potassium current (I(K(A))) in acutely dissociated rat hippocampal pyramidal neurons by using whole-cell patch clamp technique. I(K(DR)) was inhibited by galantamine in a concentration-dependent manner, while I(K(A)) remained unaffected. The IC(50) value for the blocking action of galantamine on I(K(DR)) was calculated as 2.0 microM. At the concentration of 10 microM, galantamine inhibited I(K(DR)) by 40.2% at +40 mV when depolarized from -50 mV, and shifted the activation curve and inactivation curve of I(K(DR)) to negative potential by -3.8 mV and -11.0 mV, respectively. In conclusion, galantamine potently inhibits I(K(DR)) but not I(K(A)) in rat hippocampal pyramidal neurons.
Pan
Ya-Ping
YP
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, 1 Xiannongtan Street, Beijing 100050, China.
Xu
Xiang-Hua
XH
Wang
Xiao-Liang
XL
D000818:Animals; D018929:Cell Culture Techniques; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004594:Electrophysiology; D005702:Galantamine / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D002800:Cholinesterase Inhibitors; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D005702:Galantamine