Huperzine A, a nootropic agent, inhibits fast transient potassium current in rat dissociated hippocampal neurons

Neurosci Lett. 2002 May 10;324(1):25-8. doi: 10.1016/s0304-3940(02)00167-2.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholine / pharmacology
  • Alkaloids
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Inhibitors / therapeutic use
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Humans
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Potassium Channel Blockers*
  • Potassium Channels / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes / therapeutic use
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Alkaloids
  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Potassium Channel Blockers
  • Potassium Channels
  • Sesquiterpenes
  • huperzine A
  • Acetylcholine