title: Bis(3)-tacrine inhibits the sustained potassium current in cultured rat hippocampal neurons.
abstract: Bis(3)-tacrine is a dimeric AChE inhibitor derived from tacrine with a potential to treat Alzheimer's disease. It was recently been reported to act as a fast off-rate antagonist of NMDA receptors with moderate affinity. In the present study, we aimed to explore whether bis(3)-tacrine could modulate the function of native sustained potassium current in cultured rat hippocampal neurons using whole-cell patch-clamp technique. We found that bis(3)-tacrine inhibited the amplitude of sustained potassium current in a reversible and concentration-dependent manner, with a potency two orders of magnitude higher than that of tacrine. The inhibition was voltage-independent between 0 to +60 mV. The IC(50) values for bis(3)-tacrine and tacrine inhibition of sustained potassium current were 0.45+/-0.07 and 50.5+/-4.8 microM, respectively. I-V curves showed a more potent inhibition of sustained potassium current by bis(3)-tacrine (1 microM) compared to tacrine at the same concentration. Bis(3)-tacrine hyperpolarized the activation curve of the current by 11.2 mV, albeit leaving the steady-state inactivation of the current unaffected.
authors.affiliation: Department of Physiology, School of Medicine, Jianghan University, Wuhan, People's Republic of China; Department of Anatomy, School of Medicine, Jianghan University, Wuhan, People's Republic of China. liu-yuwei@163.com.
authors.forename: R-J
authors.initials: RJ
authors.lastname: Wen
authors.forename: D
authors.initials: D
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: Y-W
authors.initials: YW
authors.lastname: Liu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D051663:Kv1.2 Potassium Channel / Q000037:antagonists & inhibitors* / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013619:Tacrine / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D051663:Kv1.2 Potassium Channel; D013619:Tacrine