Huperzine A inhibits the sustained potassium current in rat dissociated hippocampal neurons

The actions of huperzine A (HupA), a novel cholinesterase inhibitor, on the sustained potassium current were investigated in acutely dissociated hippocampal neurons of rat. HupA inhibited the current (IC(50) = 856 +/- 1 microM) with voltage-dependency. The effect was insensitive to 3 microM atropine. Tacrine (IC(50) = 43 +/- 3 microM) was 20 times more potent than HupA. HupA hyperpolarized the activation curve of the current by 16 mV, and markedly prolonged the decay time constant tau(2). HupA affected neither the steady-state inactivation of the current, nor its recovery from inactivation. The potential relevance of the inhibitory effect of HupA on the current to the treatment of Alzheimer's disease is discussed.