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.