Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / metabolism
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Acetylcholine / pharmacology
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Alkaloids
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Alzheimer Disease / drug therapy*
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Alzheimer Disease / metabolism
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Alzheimer Disease / physiopathology
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Animals
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Animals, Newborn
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Cells, Cultured
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Cholinesterase Inhibitors / pharmacology
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Cholinesterase Inhibitors / therapeutic use
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Hippocampus / cytology
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Hippocampus / drug effects*
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Hippocampus / metabolism
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Humans
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Neural Inhibition / drug effects
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Neural Inhibition / physiology*
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism
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Neuroprotective Agents / pharmacology*
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Neuroprotective Agents / therapeutic use
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Potassium Channel Blockers*
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Potassium Channels / metabolism
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Rats
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Rats, Sprague-Dawley
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Sesquiterpenes / pharmacology*
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Sesquiterpenes / therapeutic use
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Alkaloids
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Cholinesterase Inhibitors
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Neuroprotective Agents
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Potassium Channel Blockers
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Potassium Channels
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Sesquiterpenes
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huperzine A
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Acetylcholine