Huperzine A, a nootropic agent, inhibits fast transient potassium current in rat dissociated hippocampal neurons.
The actions of huperzine A (HupA), a novel cholinesterase inhibitor, on the fast transient potassium current (IA) were investigated in CA1 pyramidal neurons acutely dissociated from rat hippocampus. HupA reversibly inhibited IA (IC(50) = 914 +/- 1 microM). The effect was voltage-independent and insensitive to atropine. Tacrine was eight times more potent than HupA (IC(50) = 115 +/- 2 M), whereas huperzine B had little effect. HupA slowed down the decay of IA and its recovery from inactivation. HupA had no effect on the steady-state inactivation, but hyperpolarized the activation curve of IA by 6 mV. The results suggest that HupA may act as a blocker at the external mouth of the A channel. The potential relevance of the inhibitory effect of HupA on IA to the treatment of Alzheimer's disease has been discussed.
Li
Yang
Y
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Tai-Yuan Road, 200031, PR China.
Hu
Guo-Yuan
GY
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000470:Alkaloids; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012717:Sesquiterpenes; C050426:huperzine A; D000109:Acetylcholine